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.

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.

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.

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.

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.

Seating accuracy of removable partial denture frameworks fabricated by different digital workflows in comparison to conventional workflow.

PURPOSE: To evaluate the seating accuracy of removable partial denture (RPD) frameworks fabricated by two digital workflows involving selective laser melting (SLM) in comparison to the conventional workflow. MATERIALS AND METHODS: A Kennedy class III modification 1 partially edentulous mandibular arch was used as a master model. Three RPD framework groups were included: (1) a conventional workflow group with conventional impression and casting (CC), (2) a partial digital workflow group with conventional impression and digital fabrication (CD), and (3) a complete digital workflow group with digital impression and digital fabrication (DD). A total of 10 frameworks were produced for each group. The marginal gaps at the occlusal rests, retention arms, and reciprocating arms were measured by a traveling microscope. The data were analyzed with the one-way analysis of variance test. RESULTS: At the framework level, the most superior fit was observed for the CD group (79.5 µm) followed by DD (85.3 µm) and CC (114.2 µm) groups. The CD and DD groups were significantly superior to CC (p < 0.001). This fit pattern was consistent for the retention and reciprocating arms, while the occlusal rest fit was similar among all the groups. CONCLUSIONS: The SLM frameworks had a promising seating accuracy in comparison to conventional frameworks. The type of impression, conventional or digital, did not affect the accuracy of SLM frameworks. The differences observed in the present study are likely to be of minimal clinical significance.

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.

Impact of coronavirus disease 2019 restrictions on the efficacy of atropine 0.01% eyedrops for myopia control - Findings from the Western Australia Atropine for the Treatment of Myopia study.

This study explored the impact of short-term coronavirus disease 2019 (COVID-19) restrictions on the efficacy of atropine 0.01% eyedrops on myopia control in a multiethnic cohort of Australian children. In the Western Australia Atropine for the Treatment of Myopia study, 104 and 49 children were randomized to receive atropine 0.01% eyedrops and a placebo, respectively. We compared the 1-year myopia progression and axial elongation following the 2-month lockdown in 2020 to the same months in 2019 and 2021, i.e., the 1-year myopia progression up to May 2019-October 2019 (non-COVID-19) versus the 1-year progression up to May 2020-October 2020 (COVID-19 period), and the 1-year progression up to May 2021-October 2021 (non-COVID-19) versus the 1-year progression up to the same months in 2020. After excluding participants who withdrew, completed their treatment phase prior May 2020, or those whose study visits did not fall between May 2020 and October 2020, 65 participants (mean age at baseline = 11.8 ± 2.5 years) were included in the final analysis (49 in the treatment group; 16 in the placebo group). After correcting for age, sex, and ethnicity, there was no significant main effect of the short-term lockdown on the rate of spherical equivalent or axial length change. However, there was a lockdown × treatment interaction effect on the rate of axial elongation (P = 0.007). This was such that in the treatment group, the 1-year axial elongation was faster during lockdown by 0.056 mm compared to the nonlockdown periods (P = 0.009), while the rate of axial elongation in those on the placebo eye drops was similar during lockdown and nonlockdown. Our findings suggest that there is a decreased efficacy of low-concentration atropine even with relatively lenient restrictions lasting for a few months.

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.

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.

Choroidal Changes During and After Discontinuing Long-Term 0.01% Atropine Treatment for Myopia Control.

Purpose: Few studies have explored choroidal changes after cessation of myopia control. This study evaluated the choroidal thickness (ChT) and choroidal vascularity index (CVI) during and after discontinuing long-term low-concentration atropine eye drops use for myopia control. Methods: Children with progressive myopia (6-16 years; n = 153) were randomized to receive 0.01% atropine eye drops or a placebo (2:1 ratio) instilled daily over 2 years, followed by a 1-year washout (no eye drop use). Optical coherence tomography imaging of the choroid was conducted at the baseline, 2-year (end of treatment phase), and 3-year (end of washout phase) visits. The main outcome measure was the subfoveal ChT. Secondary measures include the CVI. Results: During the treatment phase, the subfoveal choroids in both treatment and control groups thickened by 12-14 µm (group difference P = 0.56). During the washout phase, the subfoveal choroids in the placebo group continued to thicken by 6.6 µm (95% confidence interval [CI] = 1.7 to 11.6), but those in the atropine group did not change (estimate = -0.04 µm; 95% CI = -3.2 to 3.1). Participants with good axial eye growth control had greater choroidal thickening than the fast-progressors during the treatment phase regardless of the treatment group (P < 0.001), but choroidal thickening in the atropine group's fast-progressors was not sustained after stopping eye drops. CVI decreased in both groups during the treatment phase, but increased in the placebo group after treatment cessation. Conclusions: On average, compared to placebo, 0.01% atropine eye drop treatment did not cause a differential rate of change in ChT during treatment, but abrupt cessation of long-term 0.01% atropine eye drops may disrupt normal choroidal thickening in children.

Nutritional Deficiencies and Associated Oral Health in Adolescents: A Comprehensive Scoping Review.

INTRODUCTION: The shift to processed foods in American diets has increased vitamin and mineral deficiencies among adolescents, impacting growth and health, often manifesting as oral lesions. This review study aimed to explore the link between nutritional deficiencies and adolescent oral health to improve guidance and prevent long-term issues. METHODS: A systematic review of literature from 2013 to 2023 was conducted on adolescents aged 10-19 years, using PRISMA guidelines. Searches in PubMed, Web of Science, Dentistry & Oral Sciences Source-Ebscohost, and Scopus included peer-reviewed articles, excluding reviews and non-empirical studies. Data were screened and extracted with independent reviews for accuracy. RESULTS: Malnutrition strongly correlates with poor oral health. Undernourished children have a 60% increase in dental caries, exacerbated by high sugar intake. Early malnutrition delays dental eruption, temporarily protecting against caries, while stunting and infections cause enamel defects. Chronic conditions like cerebral palsy and celiac disease worsen oral health, with risks persisting into adulthood. CONCLUSIONS: Nutritional deficiencies and oral health are interconnected, requiring integrated healthcare. Early interventions and holistic strategies can improve outcomes and reduce long-term burdens. Comprehensive health education and routine dental evaluations are essential for prevention and treatment, enhancing health across all demographics.

Addressing opioid misuse through community-engaged strategy development: study protocol of a randomized controlled trial.

BACKGROUND: Involving stakeholders in the research process facilitates collaboration, increasing understanding of factors influencing their wellbeing and motivating community action. Currently, there is a need for randomized controlled trials to evaluate the effectiveness of community-engaged research approaches for health, well-being, and engagement outcomes. In this study, we evaluate the effectiveness of both the SEED Method and a modified Delphi method in a participatory project to develop local strategies to address the opioid epidemic in three rural communities. The purpose of this study is to increase the level of evidence for community-engaged research methods through a randomized controlled trial. METHODS: Two communities will use the SEED Method and one will use a modified Delphi method. We aim to recruit a total of 144 participants (48 per community). The evaluation team will randomize participants to an intervention group or a control group. In addition, we will collect outcome data from the participatory research team members leading the projects in each county (n = 18) and from additional community members who participate in focus groups (n = 32). The primary outcome for all participants will be the change in self-reported civic engagement as measured by the total score on the Individual Mobilization Scale. DISCUSSION: In the context of participatory action to address opioid misuse in rural counties, this study will provide an understanding of the effectiveness of two community engagement methods for increasing civic engagement, as well as the extent to which participants successfully create locally tailored action strategies. The study will also explore how the observed effects differ depending on the participant's role in the project (stakeholder participant, community research team member, or focus group participant), which is an important consideration for participatory research.

Community-engaged research has become increasingly popular, yet there remains a need for randomized controlled trials that focus on testing the effectiveness of community-engaged research methods for outcomes relevant to the health, well-being, or civic engagement of individuals. Community members and researchers will benefit from data on the effectiveness of engagement methods. This will help them make decisions about which community engagement methods are best suited to project aims and participants' expectations. This research protocol describes a study comparing the effectiveness of two community engagement methods, the SEED Method and the Delphi method, and a control intervention in three rural counties. In each of the counties, participants will be randomized to an intervention group using a community-engaged method or a control group using standard survey methods. Participants will create local strategies for addressing opioid misuse and prioritize those strategies for use in community action planning. For study purposes, we define opioid misuse as a problematic pattern of using opioids (prescription or illicit). Community members participating in the study represent a range of relevant stakeholders, such as people with Opioid Use Disorder, family members of people who use opioids, community service and health care providers, substance use treatment and recovery providers, and local policymakers. In each county, the research is being conducted by a diverse team of community members led by a Cooperative Extension member. We will assess changes in the self-rated civic engagement of participants and compare the number and types of strategies created and prioritized using the three methods evaluated.

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.

Impact of the coronavirus disease 2019 pandemic on the progression, prevalence, and incidence of myopia: A systematic review.

We systematically reviewed the literature on the effects of the coronavirus disease 2019 (COVID-19) pandemic on the progression, prevalence, and incidence of myopia. A comprehensive literature search was performed on PubMed, Cochrane Central Register of Controlled Trials, and Scopus databases. Studies included in the review assessed myopia progression, prevalence, and/or incidence as the primary outcome. Of 523 articles yielded in the initial search, 23 studies (6 cross-sectional and 17 cohort) were eligible for inclusion. Sixteen of these were conducted in China and one each in Hong Kong, Turkey, Spain, Israel, India, Korea, and Tibet. Quality appraisals were conducted with the Joanna Briggs Institute Critical Appraisal Checklists. Of the included studies, a large majority reported a greater myopic shift and increase in myopia prevalence during the COVID-19 pandemic compared to the pre-COVID-19 years. All three studies on myopia incidence showed increased incidence during the COVID-19 pandemic. Myopia progression accelerated during the COVID-19 pandemic, even in individuals using low-concentration atropine eye drops in two studies but not in those using orthokeratology treatment in one study. Overall, the studies found that the COVID-19 pandemic and its associated home confinement measures generally increased myopia progression, prevalence, and incidence, even in individuals using low-concentration atropine eye drops.

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.

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

PURPOSE: 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.

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.

Macular structural integrity estimates are associated with Parkinson's disease genetic risk.

BACKGROUND: Optical coherence tomography (OCT) is a non-invasive technique to measure retinal layer thickness, providing insights into retinal ganglion cell integrity. Studies have shown reduced retinal nerve fibre layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thickness in Parkinson's disease (PD) patients. However, it is unclear if there is a common genetic overlap between the macula and peripapillary estimates with PD and if the genetic risk of PD is associated with changes in ganglion cell integrity estimates in young adults. METHOD: Western Australian young adults underwent OCT imaging. Their pRNFL, GCIPL, and overall retinal thicknesses were recorded, as well as their longitudinal changes between ages 20 and 28. Polygenic risk scores (PRS) were estimated for each participant based on genome-wide summary data from the largest PD genome-wide association study conducted to date. We further evaluated whether PD PRS was associated with changes in thickness at a younger age. To evaluate the overlap between retinal integrity estimates and PD, we annotated and prioritised genes using mBAT-combo and performed colocalisation through the GWAS pairwise method and HyPrColoc. We used a multi-omic approach and single-cell expression data of the retina and brain through a Mendelian randomisation framework to evaluate the most likely causal genes. Genes prioritised were analysed for missense variants that could have a pathogenic effect using AlphaMissense. RESULTS: We found a significant association between the Parkinson's disease polygenic risk score (PD PRS) and changes in retinal thickness in the macula of young adults assessed at 20 and 28 years of age. Gene-based analysis identified 27 genes common to PD and retinal integrity, with a notable region on chromosome 17. Expression analyses highlighted NSF, CRHR1, and KANSL1 as potential causal genes shared between PD and ganglion cell integrity measures. CRHR1 showed consistent results across multiple omics levels. INTERPRETATION: Our findings suggest that retinal measurements, particularly in young adults, could be a potential marker for PD risk, indicating a genetic overlap between retinal structural integrity and PD. The study highlights specific genes and loci, mainly on chromosome 17, as potential shared etiological factors for PD and retinal changes. Our results highlight the importance of further longitudinal studies to validate retinal structural metrics as early indicators of PD predisposition.

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.