Epidemiology and clinical relevance of persistent bacteraemia in patients with Gram-negative bloodstream infection: a retrospective cohort study.

OBJECTIVES: The risk factors and outcomes associated with persistent bacteraemia in Gram-negative bloodstream infection (GN-BSI) are not well described. We conducted a follow-on analysis of a retrospective population-wide cohort to characterize persistent bacteraemia in patients with GN-BSI. METHODS: We included all hospitalized patients >18 years old with GN-BSI between April 2017 and December 2021 in Ontario who received follow-up blood culture (FUBC) 2-5 days after the index positive blood culture. Persistent bacteraemia was defined as having a positive FUBC with the same Gram-negative organism as the index blood culture. We identified variables independently associated with persistent bacteraemia in a multivariable logistic regression model. We evaluated whether persistent bacteraemia was associated with increased odds of 30- and 90-day all-cause mortality using multivariable logistic regression models adjusted for potential confounders. RESULTS: In this study, 8807 patients were included; 600 (6.8%) had persistent bacteraemia. Having a permanent catheter, antimicrobial resistance, nosocomial infection, ICU admission, respiratory or skin and soft tissue source of infection, and infection by a non-fermenter or non-Enterobacterales/anaerobic organism were associated with increased odds of having persistent bacteraemia. The 30-day mortality was 17.2% versus 9.6% in those with and without persistent bacteraemia (aOR 1.65, 95% CI 1.29-2.11), while 90-day mortality was 25.5% versus 16.9%, respectively (aOR 1.53, 95% CI 1.24-1.89). Prevalence and odds of developing persistent bacteraemia varied widely depending on causative organism. CONCLUSIONS: Persistent bacteraemia is uncommon in GN-BSI but is associated with poorer outcomes. A validated risk stratification tool may be useful to identify patients with persistent bacteraemia.

The Influence of Vitamin D Levels on Dental Caries: A Retrospective Study of the United States Population.

(1) Background: This study examines vitamin D's impact on dental caries to inform prevention strategies, given its critical role in bone and calcium regulation, vital for dental health. (2) Methods: Data from 18,683 participants of the National Health and Nutrition Examination Survey (NHANES) 2011-2016 were analyzed. NHANES collects U.S. population data through interviews, physical exams, and tests, including vitamin D levels and dental health assessed using both the decayed, missing, and filled teeth (DMFT) index and the presence of untreated dental caries. Vitamin D levels were measured according to serum 25(OH)D concentrations, and the analyses adjusted for confounders such as body mass index (BMI) and socioeconomic status (SES) using Chi-square, Mann-Whitney U, Kruskal-Wallis tests, as well as logistic and Poisson regression. (3) Results: This study found a mean DMFT score of 7.36 and a 33.2% prevalence of untreated dental caries. A higher caries prevalence was correlated with a lower SES (p < 0.001), the male gender (p < 0.001), and a higher BMI (p < 0.001). Severe vitamin D deficiency (<25 nmol/L) doubled the risk of dental caries, with odds ratios of 2.261 and 1.953 after adjusting for demographic factors and BMI. (4) Conclusions: Our study confirms a significant relationship between low vitamin D levels and an increased risk of dental caries nationwide, even after accounting for sociodemographic factors, emphasizing the importance of maintaining sufficient vitamin D levels for preventing caries.

Evaluation of geographic variations in appendicectomy outcomes within Western Australia assessing the impact of surgical wait times and rate of negative appendicectomies in both urban and rural locations statewide.

PURPOSE: Surgery wait times after diagnosis of appendicitis are an important factor influencing the success of a patient's treatment. The proposed study will be a quantitative multicenter retrospective cohort design with the primary aim of assessing the difference between appendicectomy wait times between rural and urban hospitals in Western Australia and the effect of this on operative outcomes. Selected outcome measures will be examined by time from initial presentation at an emergency department to the patient being diagnosed and then time of diagnosis to surgery being performed. The secondary aim is to compare rates of negative appendicectomies between hospitals. METHODS: Appendicectomy patients will be identified from operating room register by medical student data collectors; then, each respective hospital's emergency room data collection will subsequently be accessed to complete case report forms based on demographics and clinical findings, pre-operative investigations, and management and follow-up. Case report forms with > 95% completeness will be accepted for pooled analysis. The expected duration of retrospective data collection will be 8 months. This study RGS6483 has received HREC approval by the Royal Perth Hospital HREC Ethics Committee, with a waiver of consent obtained and the HREC was notified of amendments to the protocol made on April 21, 2024. Dissemination of results. Data will be collected and stored online through a secure server running the Research Electronic Data Capture (REDCap) web application. No patient-identifiable data will be entered into the system. Results will subsequently be shared via scientific journal publication and presentation at relevant meetings.

Polygenic Prediction of Keratoconus and its Measures: Cross-Sectional and Longitudinal Analyses in Community-Based Young Adults.

AIM: This study evaluates the performance of a multitrait polygenic risk score (PRS) in an independent cohort to predict incident or progression of keratoconus. DESIGN: Prospective cross-sectional and cohort study METHODS: Setting: Single-center; Study population: 1478 community-based young adults (18-30 years; 51% female), including 609 (52% female) who returned for an 8-year follow-up; Observation procedures: Scheimpflug imaging (Pentacam, Oculus), genotyping and development of a multitrait PRS previously validated to predict keratoconus in older adults.; Main outcome measure: Belin/Ambrόsio enhanced ectasia display (BAD-D) score and keratoconus, defined as BAD-D ≥2.6, were each analyzed against the PRS using linear and logistic regression, respectively. RESULTS: Prevalence of keratoconus was 2.5% (95% confidence interval [CI] = 1.9-3.6) in the cross-sectional cohort. Each z-score increase in PRS was associated with worse BAD-D z-score by 0.13 (95%CI = 0.08-0.18) and 1.6 increased odds of keratoconus. The 8-year keratoconus incidence was 2.6% (95%CI = 1.3-4.0). Participants in the highest PRS decile were more likely to have incident keratoconus compared to the rest of the cohort (odds ratio = 3.85, 95%CI = 1.21-12.22). For each z-score increase in PRS, 8-year change in BAD-D z-score worsened by 0.11 (95%CI = 0.04-0.17). CONCLUSIONS: A PRS for keratoconus could be useful in predicting incident keratoconus and progression, demonstrating its potential utility in clinical settings to identify patients at high risk of postsurgery ectasia or those who may benefit most from keratoconus intervention.

Association between infectious diseases consultation and mortality in hospitalized patients with Gram-negative bloodstream infection: a retrospective population-wide cohort study.

OBJECTIVES: Data supporting routine infectious diseases (ID) consultation in Gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases. METHODS: Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1-10 days after the first positive blood culture was treated as a time-varying exposure. RESULTS: Of 30,159 patients with GN-BSI across 53 hospitals, 11,013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7-76.1%, interquartile range 19.6-41.1%). 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully-adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted HR 0.82, 95% CI 0.77-0.88, p < 0.0001; translating to absolute risk reduction of -3.8% or NNT of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source). CONCLUSIONS: Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes.

Surviving cardiac arrest after carbon monoxide poisoning treated with hyperbaric oxygen therapy.

Carbon monoxide (CO) and cyanide poisoning are frequent causes of morbidity and mortality in cases of house and industrial fires. The 14th edition of guidelines from the Undersea and Hyperbaric Medical Society does not recommend hyperbaric oxygen (HBO2) treatment in those patients who have suffered a cardiac arrest and had to receive cardiopulmonary resuscitation. In this paper, we describe the case of a 31-year-old patient who received HBO2 treatment in the setting of cardiac arrest and survived.

Persistent DNA Methylation Changes across the First Year of Life and Prenatal NO2 Exposure in a Canadian Prospective Birth Study.

BACKGROUND: Evidence suggests that prenatal air pollution exposure alters DNA methylation (DNAm), which could go on to affect long-term health. It remains unclear whether DNAm alterations present at birth persist through early life. Identifying persistent DNAm changes would provide greater insight into the molecular mechanisms contributing to the association of prenatal air pollution exposure with atopic diseases. OBJECTIVES: This study investigated DNAm differences associated with prenatal nitrogen dioxide (NO2) exposure (a surrogate measure of traffic-related air pollution) at birth and 1 y of age and examined their role in atopic disease. We focused on regions showing persistent DNAm differences from birth to 1 y of age and regions uniquely associated with postnatal NO2 exposure. METHODS: Microarrays measured DNAm at birth and at 1 y of age for an atopy-enriched subset of Canadian Health Infant Longitudinal Development (CHILD) study participants. Individual and regional DNAm differences associated with prenatal NO2 (n=128) were identified, and their persistence at age 1 y were investigated using linear mixed effects models (n=124). Postnatal-specific DNAm differences (n=125) were isolated, and their association with NO2 in the first year of life was examined. Causal mediation investigated whether DNAm differences mediated associations between NO2 and age 1 y atopy or wheeze. Analyses were repeated using biological sex-stratified data. RESULTS: At birth (n=128), 18 regions of DNAm were associated with NO2, with several annotated to HOX genes. Some of these regions were specifically identified in males (n=73), but not females (n=55). The effect of prenatal NO2 across CpGs within altered regions persisted at 1 y of age. No significant mediation effects were identified. Sex-stratified analyses identified postnatal-specific DNAm alterations. DISCUSSION: Regional cord blood DNAm differences associated with prenatal NO2 persisted through at least the first year of life in CHILD participants. Some differences may represent sex-specific alterations, but replication in larger cohorts is needed. The early postnatal period remained a sensitive window to DNAm perturbations. https://doi.org/10.1289/EHP13034.

Heart failure - An unexplored risk factor for infective endocarditis after pacemaker implantation.

BACKGROUND: With the widespread use of permanent pacemakers (PPM), and increased mortality associated with pacemaker endocarditis, it is essential to evaluate comorbidities that could potentially increase the risk of infective endocarditis (IE). Heart failure (HF), a common comorbidity, has not been well studied as an independent risk factor for development of IE in individuals with PPM. METHODS: The US National Inpatient Sample database was used to sample individuals with PPM. Patients with concomitant implantable cardioverter defibrillator, acute heart failure, history of endocarditis, intravenous drug use, prosthetic heart valves, or central venous catheter infection were excluded. Propensity matching was performed to match patients with and without HF. Pre- and post-match logistic regression was performed to assess HF as an independent risk factor for IE. A subgroup analysis was performed comparing IE rates between patients with HF with reduced (HFrEF) vs preserved (HFpEF) ejection fraction. RESULTS: Out of 333,571 patients with PPM included in the study, 121,862 (37 %) had HF. HF patients were older and had a higher prevalence of females. All comorbidities except for dental disease and cancer were more prevalent in the HF group. Patients with HF were 1.30 times more likely to develop IE [OR: 1.30 (1.16-1.47); p < 0.001]. The two cohorts were then matched for age, gender, and 20 comorbidities using a 1:1 propensity score matching algorithm. After matching, HF was still independently associated with increased risk of IE [OR: 1.62 (1.36-1.93); p < 0.001]. In our sub-group analysis, HFrEF and HFpEF patients had similar IE rates. CONCLUSION: In PPM population, HF was associated with an increased risk of IE compared to those without HF. We hypothesize that HF being a low-flow and high-inflammatory state might have contributed to this increased risk. Larger studies are required to corroborate our findings and evaluate the need for antimicrobial prophylaxis for this population.

Operant social self-administration in male CD1 mice.

RATIONALE AND OBJECTIVE: We recently introduced a model of operant social reward in which female CD1 mice lever press for access to affiliative social interaction with a cagemate peer mouse of the same sex and strain. Here we determined the generality of the operant social self-administration model to male CD1 mice who, under certain conditions, will lever press to attack a subordinate male mouse. METHODS: We trained male CD1 mice to lever press for food and social interaction with a same sex and strain cagemate peer under different fixed-ratio (FR) schedule response requirements (FR1 to FR6). We then tested their motivation to seek social interaction after 15 days of isolation in the presence of cues previously paired with social self-administration. We also determined the effect of housing conditions on operant social self-administration and seeking. Finally, we determined sex differences in operant social self-administration and seeking, and the effect of housing conditions on unconditioned affiliative and antagonistic (aggressive) social interactions in both sexes. RESULTS: Male CD1 mice lever pressed for access to a cagemate peer under different FR response requirements and seek social interaction after 15 isolation days; these effects were independent of housing conditions. There were no sex differences in operant social self-administration and seeking. Finally, group-housed CD1 male mice did not display unconditioned aggressive behavior toward a peer male CD1 mouse. CONCLUSIONS: Adult socially housed male CD1 mice can be used in studies on operant social reward without the potential confound of operant responding to engage in aggressive interactions.

Novel DNA methylation changes in mouse lungs associated with chronic smoking.

Smoking is a potent cause of asthma exacerbations, chronic obstructive pulmonary disease (COPD) and many other health defects, and changes in DNA methylation (DNAm) have been identified as a potential link between smoking and these health outcomes. However, most studies of smoking and DNAm have been done using blood and other easily accessible tissues in humans, while evidence from more directly affected tissues such as the lungs is lacking. Here, we identified DNAm patterns in the lungs that are altered by smoking. We used an established mouse model to measure the effects of chronic smoke exposure first on lung phenotype immediately after smoking and then after a period of smoking cessation. Next, we determined whether our mouse model recapitulates previous DNAm patterns observed in smoking humans, specifically measuring DNAm at a candidate gene responsive to cigarette smoke, Cyp1a1. Finally, we carried out epigenome-wide DNAm analyses using the newly released Illumina mouse methylation microarrays. Our results recapitulate some of the phenotypes and DNAm patterns observed in human studies but reveal 32 differentially methylated genes specific to the lungs which have not been previously associated with smoking. The affected genes are associated with nicotine dependency, tumorigenesis and metastasis, immune cell dysfunction, lung function decline, and COPD. This research emphasizes the need to study CS-mediated DNAm signatures in directly affected tissues like the lungs, to fully understand mechanisms underlying CS-mediated health outcomes.

Follow-up blood cultures do not reduce mortality in hospitalized patients with Gram-negative bloodstream infection: a retrospective population-wide cohort study.

OBJECTIVES: The utility of follow-up blood cultures (FUBCs) in patients with Gram-negative bloodstream infection (GN-BSI) is controversial. Observational studies have suggested significant mortality benefit but may be limited by single-centre designs, immortal time bias, and residual confounding. We examined the impact of FUBCs on mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario, Canada. METHODS: Adult patients with GN-BSI hospitalized between April 2017 and December 2021 were included. Primary outcome was all-cause mortality within 30 days. FUBC was treated as a time-varying exposure. Secondary outcomes were 90-day mortality, length of stay, and number of days alive and out of hospital at 30 and 90 days. RESULTS: Thirty-four thousand one hundred patients were included; 8807 (25.8%) patients received FUBC, of which 966 (11.0%) were positive. Median proportion of patients receiving FUBC was 18.8% (interquartile range, 10.0-29.7%; range, 0-66.1%) across 101 hospitals; this correlated with positivity and contamination rate. Eight hundred ninety (10.1%) patients in the FUBC group and 2263 (8.9%) patients in the no FUBC group died within 30 days. In the fully adjusted model, there was no association between FUBC and mortality (hazard ratio, 0.97; 95% CI, 0.90-1.04). Patients with FUBC had significantly longer length of stay (median, 11 vs. 7 days; adjusted risk ratio, 1.18; 95% CI, 1.16-1.21) and fewer number of days alive and out of hospital at 30 and 90 days. DISCUSSION: FUBC collection in patients with GN-BSI varies widely across hospitals and may be associated with prolonged hospitalization without clear survival benefit. Residual confounding may be present given the observational design. Clear benefit should be demonstrated in a randomized trial before widespread adoption of routine FUBC.

Unveiling the Hidden Stroke Threat in Patients With Atrial Fibrillation and Primary Hyperparathyroidism.

Recent American College of Cardiology (ACC), American Heart Association (AHA), American College of Clinical Pharmacy (ACCP), and Heart Rhythm Society (HRS) guidelines suggest that patients with atrial fibrillation (AF) at intermediate to low annual risk of ischemic stroke can benefit from consideration of factors that might modify their risk of stroke. The role of nontraditional risk factors, such as primary hyperparathyroidism (PHPT), remains unexplored. In our study, we investigated the potential association between PHPT and the risk of ischemic stroke in patients with AF. Using data from the Nationwide Inpatient Sample Database, a retrospective cohort study focused on the adult population with AF, we stratified the participants based on PHPT presence. Demographic information, co-morbidities, and hospitalization details were extracted using International Classification of Diseases, Tenth revision codes. Propensity score matching was applied, encompassing over 20 confounding variables, including the risk factors outlined in the CHA2DS2-VASc (Congestive heart failure (C), Hypertension (H), Age ≥75 years (A2), Diabetes Mellitus (D), Stroke/Transient Ischemic Attack (TIA)/Thromboembolism (S2), Vascular disease (V), Age 65-74 years (A), Sex category [female] (Sc)) score. Multivariate logistic regression analysis was performed after matching to assess the independent impact of PHPT as an ischemic stroke risk factor. A total of 2,051 of the identified 395,249 patients with AF had PHPT. The PHPT group had an average age of 74 years and consisted of more women (66.1% vs 53.0%). After matching, it was observed that the PHPT group had longer hospital stays (5 vs 4 days) and higher hospitalization charges ($45,126 vs $36,644). This group exhibited higher rates of ischemic stroke (6.0% vs 4.4%) and mortality (6.3% vs 4.9%). The adjusted outcomes showed a 1.4-fold increased risk for ischemic stroke and a 1.32-fold increased risk for mortality in the PHPT cohort. The subgroup analysis showed a higher incidence of mortality in men with a high CHA2DS2-VASc score. In conclusion, this study highlights a marked association between PHPT and ischemic stroke in patients with AF, independent of the conventional CHA2DS2-VASc score. The potential mechanisms implicated include vascular changes, cardiac dysfunction, and coagulation cascade alterations. The presence of PHPT should be taken into consideration when deciding the assessment of thromboembolic risk.

The late effects of haematopoietic stem cell transplants in paediatric patients: a 25 year review.

CONTEXT: A rare, large single centre study covering all long-term health outcomes of paediatric allogeneic HSCT survivors, to provide comprehensive local data, and identify gaps and future directions for improved care. OBJECTIVE: To document endocrine sequelae and other late effects of all HSCT recipients. DESIGN: Retrospective review. SETTING: Royal Children's Hospital Melbourne. PATIENTS: 384 children and adolescents received HSCT. 228 formed the study cohort; 212 were alive at commencement of data accrual. INTERVENTION: None. MAIN OUTCOME MEASURES: Incidence of endocrinopathies; fertility, growth, bone and metabolic status; subsequent malignant neoplasms (SMNs). RESULTS: Gonadotoxicity was more common in females (p<0.001). Total body irradiation (TBI) conditioning was more toxic than chemotherapy alone. All females receiving TBI or higher cyclophosphamide equivalent doses (CED) developed premature ovarian insufficiency (POI) . In males, impaired spermatogenesis +/- testicular endocrine dysfunction was associated with increasing testicular radiation exposure. Preservation of gonadal function was associated with younger age at HSCT. Of sexually active females, 22% reported spontaneous pregnancies. Short stature was common, with growth hormone axis disruption in 30% of these. Of patients exposed to thyroid radiation 51% developed nodules, 30% malignant. Metabolic disturbances included hypertension, dyslipidemias, with both excess and underweight reported. Fragility fractures occurred in 6%; avascular necrosis in 6%. 13% developed SMNs, risk continuing to rise throughout follow-up. CONCLUSIONS: We confirm gonadal dysfunction, multiple endocrine and metabolic abnormalities, thyroid cancer and SMNs, as common sequelae of HSCT, and identify gaps in management - particularly the need for informed fertility counselling and pretreatment fertility preservation, evaluation and management of bone health, and underline need for early lifestyle modification, long-term surveillance, and prospective planned studies aimed at reducing complication risk.

Myopia progression following 0.01% atropine cessation in Australian children: Findings from the Western Australia - Atropine for the Treatment of Myopia (WA-ATOM) study.

BACKGROUND: A rebound in myopia progression following cessation of atropine eyedrops has been reported, yet there is limited data on the effects of stopping 0.01% atropine compared to placebo control. This study tested the hypothesis that there is minimal rebound myopia progression after cessation of 0.01% atropine eyedrops, compared to a placebo. METHODS: Children with myopia (n = 153) were randomised to receive 0.01% atropine eyedrops or a placebo (2:1 ratio) daily at bedtime during the 2-year treatment phase of the study. In the third year (wash-out phase), all participants ceased eyedrop instillation. Participants underwent an eye examination every 6 months, including measurements of spherical equivalent (SphE) after cycloplegia and axial length (AL). Changes in the SphE and AL during the wash-out phase and throughout the 3 years of the study (treatment + wash-out phase) were compared between the treatment and control groups. RESULTS: During the 1-year wash-out phase, SphE and AL progressed by -0.41D (95% CI = -0.33 to -0.22) and +0.20 mm (95% CI = -0.46 to -0.36) in the treatment group compared to -0.28D (95% CI = 0.11 to 0.16) and +0.13 mm (95% CI = 0.18 to 0.21) in the control group. Progression in the treatment group was significantly faster than in the control group (p = 0.016 for SphE and <0.001 for AL). Over the 3-year study period, the cumulative myopia progression was similar between the atropine and the control groups. CONCLUSIONS: These findings showed evidence of rapid myopia progression following cessation of 0.01% atropine. Further investigations are warranted to ascertain the long-term effects of atropine eyedrops.

Myopia outcome study of atropine in children: Two-year result of daily 0.01% atropine in a European population.

PURPOSE: The Myopia Outcome Study of Atropine in Children (MOSAIC) is an investigator-led, double-masked, randomized controlled trial investigating the efficacy and safety of 0.01% atropine eye drops for managing myopia progression in a predominantly White, European population. METHODS: Children aged 6-16 years with myopia were randomly allocated 2:1 to nightly 0.01% atropine or placebo eye drops in both eyes for 2 years. The primary outcome was cycloplegic spherical equivalent (SE) progression at 24 months. Secondary outcomes included axial length (AL) change, safety and acceptability. Linear mixed models with random intercepts were used for statistical analyses. RESULTS: Of 250 participants enrolled, 204 (81.6%) completed the 24-month visit (136 (81.4%) treatment, 68 (81.9%) placebo). Baseline characteristics, drop-out and adverse event rates were similar between treatment and control groups. At 24 months, SE change was not significantly different between 0.01% atropine and placebo groups (effect = 0.10 D, p = 0.07), but AL growth was lower in the 0.01% atropine group, compared to the placebo group (-0.07 mm, p = 0.007). Significant treatment effects on SE (0.14 D, p = 0.049) and AL (-0.11 mm, p = 0.002) were observed in children of White, but not non-White (SE = 0.05 D, p = 0.89; AL = 0.008 mm, p = 0.93), ethnicity at 24 months. A larger treatment effect was observed in subjects least affected by COVID-19 restrictions (SE difference = 0.37 D, p = 0.005; AL difference = -0.17 mm, p = 0.001). CONCLUSIONS: Atropine 0.01% was safe, well-tolerated and effective in slowing axial elongation in this European population. Treatment efficacy varied by ethnicity and eye colour, and potentially by degree of COVID-19 public health restriction exposure during trial participation.

Social determinants of access to timely elective surgery in Ontario, Canada: a cross-sectional population level study.

BACKGROUND: Equitable access to surgical care has clinical and policy implications. We assess the association between social disadvantage and wait times for elective surgical procedures in Ontario. METHODS: We conducted a cross-sectional analysis using administrative data sets of adults receiving nonurgent inguinal hernia repair, cholecystectomy, hip arthroplasty, knee arthroplasty, arthroscopy, benign uterine surgery and cataract surgery from April 2013 to December 2019. We assessed the relation between exceeding target wait times and the highest versus lowest quintile of marginalization dimensions by use of generalized estimating equations logistic regression. RESULTS: Of the 1 385 673 procedures included, 174 633 (12.6%) exceeded the target wait time. Adjusted analysis for cataract surgery found significantly increased odds of exceeding wait times for residential instability (adjusted odd ratio [OR] 1.16, 95% confidence interval [CI] 1.11-1.21) and recent immigration (adjusted OR 1.12, 95% CI 1.07-1.18). The highest deprivation quintile was associated with 18% (adjusted OR 1.18, 95% CI 1.12-1.24) and 20% (adjusted OR 1.20, 95% CI 1.12-1.28) increased odds of exceeding wait times for knee and hip arthroplasty, respectively. Residence in areas where higher proportions of residents self-identify as being part of a visible minority group was independently associated with reduced odds of exceeding target wait times for hip arthroplasty (adjusted OR 0.82, 95% CI 0.75-0.91), cholecystectomy (adjusted OR 0.68, 95% CI 0.59-0.79) and hernia repair (adjusted OR 0.65, 95% CI 0.56-0.77) with an opposite effect in benign uterine surgery (adjusted OR 1.28, 95% CI 1.17-1.40). INTERPRETATION: Social disadvantage had a small and inconsistent impact on receiving care within wait time targets. Future research should consider these differences as they relate to resource distribution and the organization of clinical service delivery.

Natural history of infants with vitamin D deficiency in Hong Kong.

BACKGROUND AND OBJECTIVES: The usual recommended intake of vitamin D for healthy infants is 400 international unit (IU) daily. However, a high dose of vitamin D at 2000-3000 IU daily is needed for those with vitamin D deficiency (VDD). This study aimed to assess the natural history of a group of healthy infants with VDD and the associated factors for persistent VDD. METHODS AND STUDY DESIGN: Healthy infants detected to have VDD (25OHD <25 nmol/L) in a population study were followed, and their demographics and clinical data were collected. RESULTS: One hundred and thirty-one subjects (boys = 66%) were included. Their first serum 25OHD was taken at a median age of 87.5 days. None were treated with high-dose vitamin D supplements, but some have been given vitamin D at 400 IU daily. They were assessed again at the median age of 252.5 days when 15 remained to have VDD and 26 were in the insufficient range (25 - 49.9nmol/L). All persistent VDD children were on exclusive breastfeeding. Exclusive breastfeeding and no vitamin D supplementation were significant risk factors for persistent vitamin D insufficiency (<50nmol/L). CONCLUSIONS: Persistent VDD is common among infants exclusively breastfeeding and those who did not receive vitamin D supplementation.

Changes in Refractive Error During Young Adulthood: The Effects of Longitudinal Screen Time, Ocular Sun Exposure, and Genetic Predisposition.

Purpose: Changes in refractive error during young adulthood is common yet risk factors at this age are largely unexplored. This study explored risk factors for these changes, including gene-environmental interactions. Methods: Spherical equivalent refraction (SER) and axial length (AL) for 624 community-based adults were measured at 20 (baseline) and 28 years old. Participants were genotyped and their polygenic scores (PGS) for refractive error calculated. Self-reported screen time (computer, television, and mobile devices) from 20 to 28 years old were collected prospectively and longitudinal trajectories were generated. Past sun exposure was quantified using conjunctival ultraviolet autofluorescence (CUVAF) area. Results: Median change in SER and AL were -0.023 diopters (D)/year (interquartile range [IQR] = -0.062 to -0.008) and +0.01 mm/year (IQR = 0.000 to 0.026), respectively. Sex, baseline myopia, parental myopia, screen time, CUVAF, and PGS were significantly associated with myopic shift. Collectively, these factors accounted for approximately 20% of the variance in refractive error change, with screen time, CUVAF, and PGS each explaining approximately 1% of the variance. Four trajectories for total screen time were found: "consistently low" (n = 148), "consistently high" (n = 250), "consistently very high" (n = 76), and "increasing" (n = 150). Myopic shift was faster in those with "consistently high" or "consistently very high" screen time compared to "consistently-low" (P ≤ 0.031). For each z-score increase in PGS, changes in SER and AL increased by -0.005 D/year and 0.002 mm/year (P ≤ 0.045). Of the three types of screen time, only computer time was associated with myopic shift (P ≤ 0.040). There was no two- or three-way interaction effect between PGS, CUVAF, or screen time (P ≥ 0.26). Conclusions: Higher total or computer screen time, less sun exposure, and genetic predisposition are each independently associated with greater myopic shifts during young adulthood. Given that these factors explained only a small amount of the variance, there are likely other factors driving refractive error change during young adulthood.

DNA methylation is not associated with sensitization to or dietary introduction of highly allergenic foods in a subset of the CHILD cohort at age 1 year.

Background: In the first year of life, DNA methylation (DNAm) patterns are established and are particularly susceptible to exposure-induced changes. Some of these changes may leave lasting effects by persistently altering gene expression or cell type composition or function, contributing to disease. Objectives: In this discovery study, we investigated DNAm associations with sensitization to peanut, egg, or cow's milk and hypothesized that genes demonstrating DNAm differences in immune cells may play a role in the development of food sensitization. Methods: Infant sensitization (a skin prick test wheal size that is at least 2 mm greater than the negative control) was measured to peanut, egg, and cow's milk at age 1 year, and ages of food introduction were reported prospectively. PBMC DNAm was measured in blood samples at 1 year in 144 infants, oversampled for atopy or wheeze. Statistical analysis of Illumina 450k array DNAm data was conducted in R with adjustment for clinical and genetic covariables and a minimum effect size of 1%, false discovery rate of 5%, and medium-confidence false discovery rate threshold of 20%. Results: There were no DNAm differences between infants with and without peanut, egg, or cow's milk sensitization. Borderline significant sites with high effect sizes were enriched for methylation quantitative trait loci, hinting at genetic factors influencing DNAm at these sites. DNAm patterns did not differ by peanut or egg introduction before or after 12 months. Conclusion: This small pilot study did not show differences in methylation by food sensitization or introduction, but it did demonstrate DNAm patterns linked to genetic variants.