Diagnosis Codes Research Articles

Algorithms for the identification of prevalent diabetes in the All of Us Research Program validated using polygenic scores

The All of Us Research Program (AoU) is an initiative designed to gather a comprehensive and diverse dataset from at least one million individuals across the USA. This longitudinal cohort study aims to advance research by providing a rich resource of genetic and phenotypic information, enabling powerful studies on the epidemiology and genetics of human diseases. One critical challenge to maximizing its use is the development of accurate algorithms that can efficiently and accurately identify well-defined disease and disease-free participants for case-control studies. This study aimed to develop and validate type 1 (T1D) and type 2 diabetes (T2D) algorithms in the AoU cohort, using electronic health record (EHR) and survey data. Building on existing algorithms and using diagnosis codes, medications, laboratory results, and survey data, we developed and implemented algorithms for identifying prevalent cases of type 1 and type 2 diabetes. The first set of algorithms used only EHR data (EHR-only), and the second set used a combination of EHR and survey data (EHR+). A universal algorithm was also developed to identify individuals without diabetes. The performance of each algorithm was evaluated by testing its association with polygenic scores (PSs) for type 1 and type 2 diabetes. We demonstrated the feasibility and utility of using AoU EHR and survey data to employ diabetes algorithms. For T1D, the EHR-only algorithm showed a stronger association with T1D-PS compared to the EHR + algorithm (DeLong p-value = 3 × 10−5). For T2D, the EHR + algorithm outperformed both the EHR-only and the existing T2D definition provided in the AoU Phenotyping Library (DeLong p-values = 0.03 and 1 × 10−4, respectively), identifying 25.79% and 22.57% more cases, respectively, and providing an improved association with T2D PS. We provide a new validated type 1 diabetes definition and an improved type 2 diabetes definition in AoU, which are freely available for diabetes research in the AoU. These algorithms ensure consistency of diabetes definitions in the cohort, facilitating high-quality diabetes research.

Insights Into Facial Surgery Trends in the United States in the Setting of Gender Dysphoria: A National Analysis From 2012 to 2019.

Over the past decade, there has been an improvement in access to gender-affirming surgical care for the transgender population. Even with improvements, this population continues with a high level of inequity among access to specialized surgical care. While multiple studies have previously focused on trends among top and bottom surgery, this study provides trends specifically among facial gender affirmation surgery (FGAS) within the United States. The National Inpatient Sample (NIS) was utilized to identify patients who underwent FGAS from 2012 to 2019. The diagnostic codes for gender identity disorder and gender dysphoria were used to identify the desired patient population. CPT coding released in a medical policy for transgender care coverage was used to identify those who underwent FGAS. Frequency distributions from the patient population were analyzed to determine differences among characteristics. In total, 660 patients underwent FGAS from 2012 to 2019. The incidence of FGAS has increased by 1433%. Geographically, FGAS was more likely to be performed in the West and Northeast geographical regions (P<0.0001). There was a statistically significant difference in hospital length of stay and the total number of charges when stratified by race (P<0.0001 and P=0.0003), hospital location (P<0.0001 and <0.0001), and insurance type (P<0.0001 and <0.0001). The largest cohort of patients paid out-of-pocket (P<0.0001). FGAS is one of the fastest-growing GAS procedures. Currently, FGAS procedures are not equally distributed, with higher concentrations occurring among wealthier, white individuals in certain geographical regions. Future studies are warranted to understand further trends within FGAS.

Risk Score for Hepatocellular Cancer in Adults Without Viral Hepatitis or Cirrhosis

Hepatocellular carcinoma (HCC) is typically detected only at advanced stages when treatment options are limited. Most of the current HCC risk models focus on patients with viral hepatitis or diagnosed cirrhosis or require variables not routinely available in clinical care. To identify modifiable HCC risk factors in the general population and to develop a risk score to inform HCC screening and risk-factor modification interventions for high-risk individuals without viral hepatitis or decompensated cirrhosis. This cohort study analyzed demographic, clinical, laboratory, and diagnostic data from the US Department of Veterans Affairs (VA) electronic health records. Data were divided into development and validation samples. Veterans aged 30 to 95 years were included, and those with hepatitis B or C virus infection, hepatic decompensation, or prevalent HCC were excluded. Patients were followed up until the occurrence of HCC diagnosis, death, or December 31, 2021. A Cox proportional hazards regression model for 10-year risk of HCC was developed and used to create an HCC risk score, and performance in development and validation samples and in patient subgroups was evaluated. One outpatient visit date per person at least 18 months after VA entry, between October 1, 2007, and March 31, 2020, was randomly selected and used as the index date for the start of follow-up. Analyses were performed from March 2023 to May 2024. Age, sex, race and ethnicity, body mass index, liver fibrosis (detected with Fibrosis-4 Index [FIB-4]), diabetes status, smoking status, and alcohol use. First HCC diagnosis during follow-up. This information was ascertained from VA national cancer registry topography and histology codes and from International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes for the inpatient or outpatient visits. This study of 6 509 288 veterans included 6 048 917 males (92.9%), with a median (IQR) age of 65 (54-74) years, who identified as being of Hispanic (5.3%), non-Hispanic Black (15.0%), non-Hispanic White (68.9%), or other (4.6%) race and ethnicity. Overall, 15 142 patients (0.2%) developed HCC, 69.5% of whom had FIB-4 of 3.25 or lower at baseline. While FIB-4 was the most important variable, age, sex, race and ethnicity, body mass index, diabetes, smoking, and alcohol use were also informative. Discrimination in the development sample was better than FIB-4 alone (C statistic, 0.83 [95% CI, 0.82-0.85] vs 0.79 [95% CI, 0.77-0.80]). The HCC risk score performed consistently well in the validation sample and in all subgroups. A FIB-4 threshold of 3.25 would screen 5.0% of the cohort at a cost of 28 false-positives for every true-positive; a model risk score of 58 would screen 4.7% of the cohort at a cost of 23 false-positives for every true-positive. Results of this study suggest that a multivariable risk score that uses routinely available clinical data outperforms FIB-4 alone in identifying patients at risk of HCC who do not have viral hepatitis or hepatic decompensation at baseline.

Educational outcomes of children with major congenital anomalies: Study protocol for a population-based cohort study using linked hospital and education data from England

Background Major congenital anomalies (CAs) affect around 2% of live births and are a primary cause of infant mortality, childhood morbidity and long-term disability, often requiring hospitalisation and/or surgery. Children with CAs are at greater risk of lower educational attainment compared with their peers, which could be due to learning disabilities, higher rates of ill-health and school absences, or lack of adequate educational support. Our study will compare the educational attainment of children with CAs to those of their peers up to age 11 in England, using linked administrative health and education data. Methods We will analyse data from the ECHILD (Education and Child Health Insights from Linked Data) database. Children born in NHS-funded hospitals from 1st September 2003 to 31st August 2008 whose hospital records were linked to their educational records at three Key Stages (ages 4/5, 6/7 and 10/11 years) will be included. Children with different CAs, indicated by recorded hospital diagnosis codes, will be compared to children without CAs. We will compare the proportions of enrolled children who take the assessment, the proportions who reached national expected levels of attainment, and the mean standardised attainment scores for Maths and English at each Key Stage. We will describe variations in outcome by sex, ethnic minority background, region, and neighbourhood deprivation, and perform regression modelling to compare the attainment trajectories of children with and without CAs, controlling for sociodemographic factors. Ethics and dissemination Ethics approval has been obtained for the analyses of the ECHILD database. Our findings will provide information for parents regarding their children’s expected academic potential, and also enable the development of interventions to support those at risk of not doing well. We will disseminate our findings to academics, policy makers, service users and providers through seminars, peer-reviewed publications, conference abstracts and other media (lay summaries and infographics).

A Retrospective Claims Analysis of the Rate of Complications in Patients Undergoing Treatment for Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disease associated with complications that increase morbidity, such as thrombosis and chronic kidney disease. Limited data exist regarding complications among treated patients outside of clinical trials, especially for patients treated with ravulizumab. This study leverages MarketScan claims data to examine the rate of complications in patients receiving PNH treatment. Patients with a diagnosis code of PNH [International Statistical Classification of Diseases and Related Health Problems (ICD-10) diagnosis code: D59.5] between October 2015 and December 2020, aged≥18 on the date of diagnosis, who had a≥6-month follow-up period of continuous enrollment and≥1 PNH-indicated treatment on or after the first PNH diagnosis were included. Among 211 patients diagnosed with PNH being treated with eculizumab or ravulizumab between October 2015 and December 2020, the most common complications were iron deficiency (20.4% of patients), arterial embolism and thrombosis (16.1%), and chronic kidney disease (11.8%). Overall, 44.1% of patients experienced≥1 complication. The high number of patients with PNH receiving treatment who nevertheless experienced complications demonstrates significant unmet medical need. Further analysis with larger sample sizes and including newer therapies, such as pegcetacoplan and iptacopan, is required to fully understand the scope and magnitude of this unmet need.

Claims-Based Algorithm to Identify Pre-Exposure Prophylaxis Indications for Tenofovir Disoproxil Fumarate and Emtricitabine Prescriptions (2012-2014): Validation Study.

To monitor the use of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) and related medicines for pre-exposure prophylaxis (PrEP) as HIV prevention using commercial pharmacy data, it is necessary to determine whether TDF/FTC prescriptions are used for PrEP or for some other clinical indication. This study aimed to validate an algorithm to distinguish the use of TDF/FTC for HIV prevention or infectious disease treatment. An algorithm was developed to identify whether TDF/FTC prescriptions were for PrEP or for other indications from large-scale administrative databases. The algorithm identifies TDF/FTC prescriptions and then excludes patients with International Classification of Diseases (ICD)-9 diagnostic codes, medications, or procedures that suggest indications other than for PrEP (eg, documentation of HIV infection, chronic hepatitis B, or use of TDF/FTC for postexposure prophylaxis). For evaluation, we collected data by clinician assessment of medical records for patients with TDF/FTC prescriptions and compared the assessed indication identified by the clinician review with the assessed indication identified by the algorithm. The algorithm was then applied and evaluated in a large, urban, community-based sexual health clinic. The PrEP algorithm demonstrated high sensitivity and moderate specificity (99.6% and 49.6%) in the electronic medical record database and high sensitivity and specificity (99% and 87%) in data from the urban community health clinic. The PrEP algorithm classified the indication for PrEP in most patients treated with TDF/FTC with sufficient accuracy to be useful for surveillance purposes. The methods described can serve as a basis for developing a robust and evolving case definition for antiretroviral prescriptions for HIV prevention purposes.

Association of Homelessness and Unstable Housing With Cardiovascular Care Utilization Among Veterans.

Veterans are disproportionately more likely to experience homelessness and unstable housing (HUH) compared with the general population. Cardiovascular disease is the leading cause of death among Veterans experiencing HUH. We aimed to understand whether HUH status among Veterans with preexisting cardiovascular disease was associated with disparities in cardiovascular care access and utilization. Retrospective study of all Veterans with preexisting cardiovascular disease between 2017 and 2019 using Veterans Affairs Corporate Data Warehouse and Homeless registry data. Primary outcomes were annual outpatient visits for cardiovascular disease management and visits with cardiovascular disease-related specialists. Secondary outcomes included cardiovascular disease-related procedures and emergency department visits and hospitalizations. HUH status was determined based on response to a screener, diagnostic codes, or use of homelessness services, and outcomes were assessed in the first year HUH status was determined. After applying inverse probability of treatment weighting, negative binomial and logistic regression models were fit to estimate the association between experiencing HUH and the outcomes of interest. Among 1 357 973 Veterans (mean age, 71.6 [SD=10.6] years; 2.5% female) with preexisting cardiovascular disease, 56 093 were identified as experiencing HUH during the study period. Veterans experiencing HUH had fewer outpatient visits for cardiovascular disease management or with cardiovascular disease-related specialists (4.3% [95% CI, 2.5%-6.1%] and 14.1% [95% CI, 12.5%-15.8%], respectively) compared with housed Veterans. HUH status was associated with lower rates of receiving certain procedures including coronary artery bypass graft, lower extremity revascularization, and carotid artery stenosis interventions and higher rates of all-cause and cardiovascular emergency department visits and hospitalizations. Veterans with chronic cardiovascular conditions experiencing HUH had lower rates of outpatient visits for cardiovascular disease management and higher rates of emergency department visits and hospitalizations. Given the disproportionate burden of cardiovascular disease in this population, interventions to improve access to cardiovascular care are needed.

Who Gets a Code for Obesity? Reliability, Use, and Implications of Combining International Classification of Diseases-Based Obesity Codes, 2014-2021.

Background: Many studies rely on the International Classification of Diseases, 9th or 10th Revision, Clinical Modification codes to define obesity in electronic health records data. While prior studies found misclassification and low sensitivity of codes for pediatric obesity, it remains unclear whether this misclassification is random and what are the implications of combining different code types to define obesity. Methods: We assessed prevalence, sensitivity, and specificity of obesity codes among 7.4 million children aged 2-19 years over 2014-2021. Among those with obesity in 2021, we estimated the probability of receiving any code or a specific code type by patient characteristics. Results: Obesity code utilization increased in prevalence from 3.9% in 2014 to 9.8% in 2021; prevalence of obesity based on BMI increased from 17.4% to 20.5%. Code sensitivity increased from 19.8% to 40.8%. Among children with obesity in 2021, those with severe obesity (reference: no severe obesity) and chronic disease (reference: no chronic disease) were more likely to get a code, and the highest likelihood was associated with obesity diagnosis codes (vs. status codes). Conclusions: Despite increases, obesity code utilization remained low. Obesity code misclassification is not random and certain child characteristics (e.g., severe obesity or chronic disease) are associated with a higher probability of getting a code. There are also significant differences by code type; thus, caution should be taken before combining obesity codes as a proxy for obesity status, especially in longitudinal analyses. More universal documentation of obesity may improve the quality of care and the use of these data for evaluation and research purposes.

Time trends in incidence of pilonidal sinus disease from 1996 to 2021: A Danish population-based cohort study.

Pilonidal sinus disease (PSD) is a common condition, but no data on disease occurrence exist outside highly selected settings. The aim of this study was to assess time trends in the incidence of PSD in a nationwide setting. Using data from nationwide Danish registries, we identified 48 247 patients recorded with diagnostic or surgical procedure codes representing PSD between 1996 and 2021. We stratified by sex and computed the age-adjusted and age-specific incidence rate, comparing 5-year intervals with the incidence rate ratio (IRR). The overall incidence of PSD increased from 26.1 to 39.6/100 000 person-years (PY) from the period 1996-2000 to the period 2016-2021 (IRR 1.52, 95% CI 0.78-2.94). The incidence increased from 35.8 to 56.9/100 000 PY (IRR 1.59, 95% CI 0.52-4.89) in male patients and from 16.4 to 22.5/100 000 PY (IRR 1.37, 95% CI 0.68-2.76) in female patients. The peak of age-specific incidence was 215.7/100 000 PY (95% CI 206.1-245.4) among 20-year-old men and 107.9/100.000 PY (95% CI 100.0-114.0) among 18-year-old women. Over the study period, the median age at first hospital contact decreased from 27 years [interquartile range (IQR) 22-34 years) to 25 years (IQR 20-34 years) in men but remained stable around 23 years (IQR 18-32 years) in women. However, for both sexes, the highest increase in incidence was seen in early adolescence. The incidence of PSD has increased significantly over the last decades. The increase is driven primarily by men and boys, with the highest increase in incidence seen in early adolescence. The increased burden of disease is not reflected in the literature, and more studies are warranted to understand the drivers of this development.

Insights into young-onset dementia hospitalizations: An 8-year nationwide study using administrative data

ObjectiveTo characterize all Portuguese public hospitalizations of patients aged < 65 years with a primary or secondary diagnosis of dementia, based on ICD-9-CM coding. MethodsA retrospective observational study was conducted using a nationwide database encompassing all hospitalizations occurred in Portuguese mainland public hospitals with discharge from 2008 to 2015. Hospitalizations of patients aged 35–64 years with primary or secondary diagnoses of dementia were selected based on ICD-9-CM codes 290.1X-290.4X, 291.2, 292.82, 294.1X, 294.2X, 331.0, 331.1X, 331.82, 333.4 and 046.1, excluding diagnostic codes 317-319, 330.X, 343, 758.0-758.3 and 759.3. Information on age, sex, primary diagnosis, comorbidities (secondary diagnosis), type of admission, length of stay (LoS), in-hospital mortality, suicide attempts, discharge destination, readmissions and dementia etiology was collected. ResultsFrom 7971 hospitalizations, for 5682 inpatients, the median age was 57.3 years (SD±6.5) and 61.8% were of male patients. Vascular dementia was the most prevalent etiology, followed by Alzheimer's disease. Most admissions were urgent and had a primary diagnosis of ‘Delirium, dementia and other cognitive disorders’, followed by pneumonia and alcohol-related disorders. Dementia, cerebrovascular disease and diabetes were the most common comorbidities. Overall, 55.4% of admissions were first-time admissions during the study period and the median LoS was 10.0 days (Q1;Q3: 5.0;20.0). Suicide attempts were recorded in 0.6% of the episodes. The in-hospital mortality rate was 9.2% and most patients were discharged home (80.2%). ConclusionsThis study describes the complexity and strain of young-onset dementia hospitalizations providing a detailed overview and recommendations for further research and tailored interventions.

Burden of infant group B Streptococcus disease and impact of maternal screening and antibiotic prophylaxis in Ontario, Canada: a population-based cohort study

Group B Streptococcus (GBS) significantly contributes to neonatal sepsis and meningitis, with varying disease rates reported globally and limited population-based data. We estimated infant GBS disease burden in Ontario, Canada and assessed the association of maternal GBS screening (35-37 weeks' gestation) and intrapartum antibiotic prophylaxis (IAP) provision with infant disease rates. Our population-based cohort study included pregnant individuals and their offspring from April 2012 to March 2018, utilising the provincial birth registry linked to health administrative data. GBS cases were ascertained through culture results and diagnostic codes. We calculated incidence rates for early-onset disease (EOD: 0-6 days), late-onset disease (LOD: 7-89 days), and ultra-LOD (ULOD: 90-365 days). Adjusted incidence rate ratios (aIRR) were derived via log-binomial regression to compare infant GBS rates according to screening and IAP-receipt. Among 776,148 liveborn infants, we identified 803 with GBS, with multiples exhibiting a threefold incidence increase. Incidence rates of EOD, LOD and ULOD were 0.49, 0.46 and 0.07 per 1000 livebirths, respectively. Of eligible pregnancies, 94% were screened; 23% screened positive, and 81% of them received IAP. Nearly 12% of term EOD infants had mothers who missed IAP despite screening positive. Maternal screening was associated with lower rates of any infant GBS disease (aIRR: 0.60; 95% CI: 0.45, 0.80). Among screen-positive births, IAP-receipt was associated with reduced rates of EOD (aIRR: 0.72, 95% CI: 0.48, 1.29) and LOD/ULOD (aIRR: 0.69; 95% CI: 0.46, 1.05), but confidence intervals included 1.0. Our study, the largest Canadian investigation into infant GBS disease, highlights both widespread adoption and ongoing challenges of the current prevention strategy. Canadian Institutes of Health Research.

Cohort profile: the Nanjing Diabetes Cohort database – a population-based surveillance cohort

PurposeTo study epidemiology, complications, risk factors, clinical course and treatment patterns of diabetes, the Nanjing Diabetes Cohort (NDC) was established using anonymised electronic health records from 650 hospitals and primary...

Pneumatic Retinopexy for Rhegmatogenous Retinal Detachment Outcomes: IRIS® Registry (Intelligent Research in Sight) Analysis

PurposeTo determine treatment patterns and outcomes of pneumatic retinopexy (PnR) for rhegmatogenous retinal detachments (RRD). DesignRetrospective cohort analysis using IRIS® Registry (Intelligent Research in Sight) database. ParticipantsPatients with RRD treated by PnR from 2013-2022. MethodsCases were identified using International Classification of Diseases, Ninth and Tenth Revisions (ICD-9, ICD-10) diagnostic codes. Surgical procedures were identified using Current Procedural Terminology (CPT) codes for type of RRD repair. Baseline demographic information included age, sex, race and ethnicity, geographic region, smoking status, and health insurance type. Main Outcome MeasuresPrimary outcomes for PnR included single-operation success (SOS) and failure (SOF), change in visual acuity at 9-12 months, rates of complications, rates of secondary procedure following SOF, and outcome by phakic status. Results13,302 unique eyes were analyzed (median age, 64 years, 61.56% male). Overall SOS for primary PnR was 59.82%. The mean BCVA at 9-12 months following PR was LogMAR 0.44 (95% CI: 0.42, 0.46) for SOF eyes, compared to 0.23 (95% CI: 0.22, 0.25) for SOS eyes (P < 0.001). Complications of PR included vitreous hemorrhage (9.1%), ERM (45.17%), proliferative vitreoretinopathy (0.98%), and endophthalmitis (0.14%). Of the 40.18% of eyes with SOF, 81% required either secondary PnR, scleral buckle (SB), vitrectomy (VTX), or complex detachment repair (CDR), whereas the remaining eyes required more than one of these secondary procedures. SOS for phakic eyes was 64.50% versus 53.93% for pseudophakic eyes (P < 0.001). ConclusionsIRIS Registry data reveal real-world outcomes and utilization patterns of PnR for RRD. Overall SOS for primary PnR was 59.82%, which is lower than other cited rates in the literature. Pseudophakic eyes were more likely to fail primary PnR. It is important to counsel patients on risks of the procedure when obtaining informed consent.

Bias in medical AI: Implications for clinical decision-making.

Biases in medical artificial intelligence (AI) arise and compound throughout the AI lifecycle. These biases can have significant clinical consequences, especially in applications that involve clinical decision-making. Left unaddressed, biased medical AI can lead to substandard clinical decisions and the perpetuation and exacerbation of longstanding healthcare disparities. We discuss potential biases that can arise at different stages in the AI development pipeline and how they can affect AI algorithms and clinical decision-making. Bias can occur in data features and labels, model development and evaluation, deployment, and publication. Insufficient sample sizes for certain patient groups can result in suboptimal performance, algorithm underestimation, and clinically unmeaningful predictions. Missing patient findings can also produce biased model behavior, including capturable but nonrandomly missing data, such as diagnosis codes, and data that is not usually or not easily captured, such as social determinants of health. Expertly annotated labels used to train supervised learning models may reflect implicit cognitive biases or substandard care practices. Overreliance on performance metrics during model development may obscure bias and diminish a model's clinical utility. When applied to data outside the training cohort, model performance can deteriorate from previous validation and can do so differentially across subgroups. How end users interact with deployed solutions can introduce bias. Finally, where models are developed and published, and by whom, impacts the trajectories and priorities of future medical AI development. Solutions to mitigate bias must be implemented with care, which include the collection of large and diverse data sets, statistical debiasing methods, thorough model evaluation, emphasis on model interpretability, and standardized bias reporting and transparency requirements. Prior to real-world implementation in clinical settings, rigorous validation through clinical trials is critical to demonstrate unbiased application. Addressing biases across model development stages is crucial for ensuring all patients benefit equitably from the future of medical AI.

Health care resource utilization and costs across stages of amyotrophic lateral sclerosis in the United States.

People living with ALS (plwALS) experience motor control loss, speech/swallowing difficulties, respiratory insufficiency, and early death. Advancing disease stage is typically associated with a greater burden on the health care system, and delays in diagnosis can result in substantial health care resource utilization (HCRU). To estimate HCRU and cost burden of plwALS across disease stages from a US payer perspective we assessed HCRU and costs in early-, mid-, and late-stage ALS. Using insurance claims data from the IBM MarketScan Databases between January 2013 and December 2019, we identified plwALS as having at least 2 claims at least 27 days apart with an ALS International Classification of Diseases, Ninth or Tenth Revision diagnosis code (335.20/G12.21) or at least 1 ALS diagnosis code and prescription filled for riluzole/edaravone. Eligible plwALS were aged at least 18 years and had at least 12 months of enrollment data before and at least 6 months after the index date (date diagnosis criteria met). plwALS were grouped into disease stages using an ALS severity-based staging algorithm developed using ALS symptom and staging survey data from 142 neurologists reporting on 880 plwALS. The starting date of each severity stage was defined as the first date of an ALS symptom within the early-, mid-, and late-stage categories, respectively. The ending date for a severity stage was defined as the day before the first date of an ALS symptom from a more severe category. plwALS could transition to more severe stages, with reverse transition of severity excluded. Mixed regression modeling was used to assess differences in HCRU and costs per person-year between severity stages, adjusted for age and sex. 2,273 plwALS were included in the total ALS study sample, with 1,215 early-stage, 1,511 midstage, and 1,186 late-stage plwALS. 90% of early-stage plwALS had ALS symptoms before diagnosis, and 27% of late-stage plwALS had a late-stage symptom before diagnosis. In the evaluation period, later-stage ALS groups had more overall hospital admissions (early = 0.15, middle = 0.23, and late = 0.74; P < 0.01), outpatient visits/service (early = 26.81, middle = 32.78, and late = 48.54; P < 0.01), emergency department visits (early = 0.46, middle = 0.69, and late = 1.03; P < 0.01), and total prescription count (early = 9.23, middle = 11.37, and late = 12.72; P < 0.01) over 12 months. Annualized costs increased as ALS progressed (early = $31,411, middle = $51,481, and late = $121,903; P < 0.01), which was primarily driven by higher frequency of and cost per hospital admission. HCRU and costs increased with ALS progression, with diagnosis frequently occurring even after experiencing late-stage symptoms. These findings highlight the potential value of delaying progression into a more resource-intensive stage by diagnosing and adequately treating plwALS earlier in the disease course.

Impact of CCR5Δ32 on the risk of infection, Staphylococcus aureus carriage, and plasma concentrations of chemokines in Danish blood donors

The CC chemokine receptor 5 (CCR5) is a suggested receptor for Staphylococcus aureus leukotoxin ED. Homozygosity for the Δ32 deletion (CCR5Δ32) protects against human immunodeficiency virus infection and possibly also against leukotoxin ED. We examined the impact of CCR5Δ32 on the susceptibility to S.aureus infection, all-cause infections, and S.aureus nasal carriage, respectively, and on the concentrations of circulating chemokines in blood donors. We included 95,406 participants from the Danish Blood Donor Study (DBDS) genotyped for >650,000 single nucleotide polymorphisms. The CCR5Δ32 (rs333, MAF: 0.12) was imputed from a reference panel and validated. Infectious outcomes were identified by diagnosis codes and redeemed prescription of antibiotics in national health registers. Data on S.aureus nasal carriage and forty-seven inflammatory biomarkers were available for 6721 and 7811 participants, respectively. Cox, logistic, and linear regression models adjusted for relevant confounders were used to explore said associations. During more than 700,000 person-years of observation, we found that CCR5Δ32 was associated with neither an increased risk of redeemed dicloxacillin, hospital-treated S.aureus-associated infection (replicated in 345,996 Icelanders), redeemed antibiotics, all-cause infection, and nor with S.aureus nasal carriage. We discovered an association between CCR5Δ32 and elevated CCL4 concentrations, which were 1.26-fold higher in Δ32-heterozygotes (95%-CI: 1.23-1.30) and 2.64-fold higher in Δ32-homozygotes (95%-CI: 2.41-2.90) compared with wildtype homozygotes. Conversely, concentrations of CCL2, CXCL-10, and CCL11 were slightly lower among Δ32-heterozygotes. Results from this CCR5Δ32 high-prevalent cohort do not support the idea that CCR5Δ32 affects the risk of S.aureus carriage or infection to any relevant degree, in this northern European context. CCL4 was the main chemokine affected by CCR5Δ32 and was observed in higher concentration among Δ32-carriers. This study cannot rule out that S.aureus is a previous driver of CCR5Δ32 selection. The Health Research Fund of Central Denmark Region, Aarhus University, Danish Administrative Regions, Bio- and Genome Bank Denmark, Danish Blood Donor Research Foundation, Aase & Ejnar Danielsens Foundation, Højmosegård Grant, National Institute of Allergy and Infectious Diseases, and A.P. Møller Foundation for the Advancement of Medical Science.

Delayed fixation of distal radial fractures beyond three weeks after initial failed closed reduction increases the odds of reoperation.

We aimed to compare reoperations following distal radial fractures (DRFs) managed with early fixation versus delayed fixation following initial closed reduction (CR). We used administrative databases in Ontario, Canada, to identify DRF patients aged 18 years or older from 2003 to 2016. We used procedural and fee codes within 30 days to determine which patients underwent early fixation (≤ seven days) or delayed fixation following CR. We grouped patients in the delayed group by their time to definitive fixation (eight to 14 days, 15 to 21 days, and 22 to 30 days). We used intervention and diagnostic codes to identify reoperations within two years. We used multivariable regression to compare the association between early versus delayed fixation and reoperation for all patients and stratified by age (18 to 60 years and > 60 years). We identified 14,960 DRF patients, 8,339 (55.7%) of whom underwent early surgical fixation (mean 2.9 days (SD 1.8)). In contrast, 4,042 patients (27.0%) underwent delayed fixation between eight and 14 days (mean 10.2 days (SD 2.2)), 1,892 (12.7%) between 14 and 21 days (mean 17.5 days (SD 1.9)) and 687 (4.6%) > 21 days (mean 24.8 days (SD 2.4)) post-fracture. Patients who underwent delayed fixation > 21 days post-fracture had a higher odds of reoperation (odds ratio (OR) 1.33 (95% CI 1.11 to 1.79) vs early fixation). This worsened for patients aged > 60 years (OR 1.69 (95% CI 1.11 to 2.79)). We found no difference in the odds of reoperation for patients who underwent delayed fixation within eight to 14 or 15 to 21 days post-fracture (vs early fixation). These data suggest that DRF patients with fractures with unacceptable reduction following CR should be managed within three weeks to avoid detrimental outcomes. Prospective studies are required to confirm these findings.

Understanding the epidemiology of metabolic dysfunction-associated steatotic liver disease is essential for its management: need for attention to accurate diagnostic coding and classification

Understanding the epidemiology of metabolic dysfunction-associated steatotic liver disease is essential for its management: need for attention to accurate diagnostic coding and classification

Self-reported physical activity and gait in older adults without dementia: A longitudinal study.

Physical activity (PA) is associated with higher gait speed. We aimed to examine the associations between PA and change in spatial and temporal gait measures as well as fall risk in community-dwelling individuals free of dementia. Longitudinal study among 4173 individuals aged ≥50 years (mean age 71 years; 2078 males; median follow-up 4 years) enrolled in the Mayo Clinic Study of Aging. Self-reported late-life PA was used to calculate overall PA and moderate-vigorous PA (MVPA) scores. Gait was assessed using GAITRite® and Zeno™ systems. Incident falls information was based on diagnostic codes retrieved from medical records. We ran linear mixed effects models to examine associations between z-scored PA variables and longitudinal gait parameters, adjusted for age, sex, education, body mass index (BMI), medical comorbidities, and including interactions between PA and time since baseline. In secondary analyses, we calculated Cox Proportional hazard models with age as time scale predicting incident falls by PA, adjusting for sex, education, BMI, medical comorbidities, and falls history. At baseline, higher PA was associated with higher velocity (overall PA: estimate 2.9935; MVPA: 2.2961; p < 0.001), higher cadence (overall PA: 1.0665; MVPA: 0.9073; p < 0.001), greater stride length (overall PA: 2.0805; MVPA: 1.4726; p < 0.001), shorter double support time (overall PA: -0.0257; MVPA: -0.0205; p < 0.001), and lower stance time variability (overall PA: -0.0204, p < 0.001; MVPA: -0.0152; p = 0.006). Overall PA was longitudinally associated with less decline in cadence, and MVPA with less increase in intraindividual stance time variability. Overall PA (Hazard ratio 0.892, 95% confidence interval 0.828-0.961, p = 0.003) and MVPA (HR 0.901; 95% CI 0.835-0.973, p = 0.008) were associated with a decreased risk of incident falls. Late-life PA was associated with favorable gait outcomes and decreased risk of incident falls. Thus, late-life PA may help to maintain gait performance and decrease fall risk in old age.

Trends in COVID-19-Attributable Hospitalizations Among Adults With Laboratory-Confirmed SARS-CoV-2-COVID-NET, June 2020 to September 2023.

Screening for SARS-CoV-2 infection among hospital admissions made interpretation of COVID-19 hospitalization data challenging as SARS-CoV-2-positive persons with mild or asymptomatic infection may be incorrectly identified as COVID-19-associated hospitalizations. The study objective is to estimate the proportion of hospitalizations likely attributable to COVID-19 among SARS-CoV-2-positive hospitalized patients. A sample of laboratory-confirmed SARS-CoV-2-positive hospitalizations from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) from June 2020 to September 2023 was analyzed, with a focus on July 2022 to September 2023. Likely COVID-19-attributable hospitalizations were defined as hospitalizations among SARS-CoV-2-positive non-pregnant adults ages ≥ 18 years with COVID-19-related presenting complaint, treatment, or discharge diagnosis. Among 44,816 sampled hospitalizations, 90% met the definition of likely COVID-19-attributable. Among the 9866 admissions occurring during July 2022 to September 2023, 86% were likely COVID-19-attributable; 87% had a COVID-19-related presenting complaint, 64% received steroids or COVID-19-related treatment, 47% had respiratory- and 10% had coagulopathy-related discharge diagnoses, and 39% had COVID-19 as the principal discharge diagnosis code. More than 70% met ≥ 2 criteria. Compared with likely COVID-19-attributable hospitalizations, SARS-CoV-2-positive patients who did not meet the case definition were more likely to be ages 18-49 years (27% vs. 13%), have no underlying medical conditions (14% vs. 4%), or be asymptomatic for COVID-19 upon admission (46% vs. 10%) (all p < 0.05). Most hospitalizations among SARS-CoV-2-positive adults in a recent period were likely attributable to COVID-19. COVID-19-attributable hospitalizations are less common among younger SARS-CoV-2-positive hospitalized adults but still account for nearly three quarters of all admissions among SARS-CoV-2-positive adults in this age group.