Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity - IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

Background: Assessing COVID-19 vaccine effectiveness (VE) and severity of SARS-CoV-2 variants can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial genomic divergence from co-circulating XBB lineages. Methods: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated the effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. Results: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. Conclusions: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB lineage hospitalizations.

Epidemiology of RSV in Adults and Children with Medically-Attended Acute Respiratory Illness over Three Seasons.

BACKGROUND: Data on the true prevalence of RSV among medically-attended acute respiratory illnesses (MAARI) has been limited by the lack of regular clinical testing of mild to moderate illnesses. Here we present a prospective evaluation of the epidemiology of RSV-associated MAARI across age groups and multimorbidity status over three seasons, which is informative in light of the recommendations for shared decision-making for vaccination in older adults. METHODS: Ambulatory patients ≥6 months of age meeting a common MAARI case definition were prospectively enrolled in the Michigan Ford Influenza Vaccine Effectiveness (MFIVE) study, a subsite of the US Influenza Vaccine Effectiveness Network. All participants were tested by nasal-throat swab for RSV and influenza, including subtype, independently from clinician-directed testing. Participant illness characteristics and calculated Multimorbidity-Weighted Index (MWI) were collected by in-person survey and electronic medical record review. RESULTS: Over three surveillance seasons (fall 2017 to spring 2020), 9.9% (n=441) of 4,442 participants had RSV detected. RSV-associated MAARI was more prevalent than influenza for participants 6 months-4 years of age. Adults with RSV-MAARI had higher median MWI scores overall compared to influenza-MAARI and controls with neither virus (1.62, 0.40, and 0.64, respectively). CONCLUSIONS: RSV is a significant, underrecognized cause of MAARI in both children and adults presenting for ambulatory care. Multimorbidity is an important contributor to RSV-associated MAARI in outpatient adults, providing information to support shared clinical decision-making for vaccination.

Severity of Respiratory Syncytial Virus vs COVID-19 and Influenza Among Hospitalized US Adults.

Importance: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making. Objective: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status. Design, Setting, and Participants: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 US states from February 1, 2022, to May 31, 2023. Clinical data during each patient's hospitalization were collected using standardized forms. Data were analyzed from August to October 2023. Exposures: RSV, SARS-CoV-2, or influenza infection. Main Outcomes and Measures: Using multivariable logistic regression, severity of RSV disease was compared with COVID-19 and influenza severity, by COVID-19 and influenza vaccination status, for a range of clinical outcomes, including the composite of invasive mechanical ventilation (IMV) and in-hospital death. Results: Of 7998 adults (median [IQR] age, 67 [54-78] years; 4047 [50.6%] female) included, 484 (6.1%) were hospitalized with RSV, 6422 (80.3%) were hospitalized with COVID-19, and 1092 (13.7%) were hospitalized with influenza. Among patients with RSV, 58 (12.0%) experienced IMV or death, compared with 201 of 1422 unvaccinated patients with COVID-19 (14.1%) and 458 of 5000 vaccinated patients with COVID-19 (9.2%), as well as 72 of 699 unvaccinated patients with influenza (10.3%) and 20 of 393 vaccinated patients with influenza (5.1%). In adjusted analyses, the odds of IMV or in-hospital death were not significantly different among patients hospitalized with RSV and unvaccinated patients hospitalized with COVID-19 (adjusted odds ratio [aOR], 0.82; 95% CI, 0.59-1.13; P = .22) or influenza (aOR, 1.20; 95% CI, 0.82-1.76; P = .35); however, the odds of IMV or death were significantly higher among patients hospitalized with RSV compared with vaccinated patients hospitalized with COVID-19 (aOR, 1.38; 95% CI, 1.02-1.86; P = .03) or influenza disease (aOR, 2.81; 95% CI, 1.62-4.86; P < .001). Conclusions and Relevance: Among adults hospitalized in this US cohort during the 16 months before the first RSV vaccine recommendations, RSV disease was less common but similar in severity compared with COVID-19 or influenza disease among unvaccinated patients and more severe than COVID-19 or influenza disease among vaccinated patients for the most serious outcomes of IMV or death.

Post-recovery health domain scores among outpatients by SARS-CoV-2 testing status during the pre-Delta period.

BACKGROUND: Symptoms of COVID-19 including fatigue and dyspnea, may persist for weeks to months after SARS-CoV-2 infection. This study compared self-reported disability among SARS-CoV-2-positive and negative persons with mild to moderate COVID-19-like illness who presented for outpatient care before widespread COVID-19 vaccination. METHODS: Unvaccinated adults with COVID-19-like illness enrolled within 10 days of illness onset at three US Flu Vaccine Effectiveness Network sites were tested for SARS-CoV-2 by molecular assay. Enrollees completed an enrollment questionnaire and two follow-up surveys (7-24 days and 2-7 months after illness onset) online or by phone to assess illness characteristics and health status. The second follow-up survey included questions measuring global health, physical function, fatigue, and dyspnea. Scores in the four domains were compared by participants' SARS-CoV-2 test results in univariate analysis and multivariable Gamma regression. RESULTS: During September 22, 2020 - February 13, 2021, 2712 eligible adults were enrolled, 1541 completed the first follow-up survey, and 650 completed the second follow-up survey. SARS-CoV-2-positive participants were more likely to report fever at acute illness but were otherwise comparable to SARS-CoV-2-negative participants. At first follow-up, SARS-CoV-2-positive participants were less likely to have reported fully or mostly recovered from their illness compared to SARS-CoV-2-negative participants. At second follow-up, no differences by SARS-CoV-2 test results were detected in the four domains in the multivariable model. CONCLUSION: Self-reported disability was similar among outpatient SARS-CoV-2-positive and -negative adults 2-7 months after illness onset.

Structural differences contributing to sex-specific associations between FN BMD and whole-bone strength for adult White women and men.

Hip areal BMD (aBMD) is widely used to identify individuals with increased fracture risk. Low aBMD indicates low strength, but this association differs by sex with men showing greater strength for a given aBMD than women. To better understand the structural basis giving rise to this sex-specific discrepancy, cadaveric proximal femurs from White female and male donors were imaged using nano-CT and loaded in a sideways fall configuration to assess strength. FN pseudoDXA images were generated to identify associations among structure, aBMD, and strength that differ by sex. Strength correlated significantly with pseudoDXA aBMD for females (R2 = 0.468, P < .001) and males (R2 = 0.393, P < .001), but the elevations (y-intercepts) of the linear regressions differed between sexes (P < .001). Male proximal femurs were 1045 N stronger than females for a given pseudoDXA aBMD. However, strength correlated with pseudoDXA BMC for females (R2 = 0.433, P < .001) and males (R2 = 0.443, P < .001) but without significant slope (P = .431) or elevation (P = .058) differences. Dividing pseudoDXA BMC by FN-width, total cross-sectional area, or FN-volume led to significantly different associations between strength and the size-adjusted BMC measures for women and men. Three structural differences were identified that differentially affected aBMD and strength for women and men: First, men had more bone mass per unit volume than women; second, different cross-sectional shapes resulted in larger proportions of bone mass orthogonal to the DXA image for men than women; and third, men and women had different proportions of cortical and trabecular bone relative to BMC. Thus, the proximal femurs of women were not smaller versions of men but were constructed in fundamentally different manners. Dividing BMC by a bone size measure was responsible for the sex-specific associations between hip aBMD and strength. Thus, a new approach for adjusting measures of bone mass for bone size and stature is warranted.

Development and validation of new multimorbidity-weighted index for ICD-10-coded electronic health record and claims data: an observational study.

OBJECTIVE: Map multimorbidity-weighted index (MWI) conditions to International Classification of Diseases, 10th Revision (ICD-10), expand the conditions and codes to develop a new ICD-10-coded MWI (MWI-ICD10) and updated MWI-ICD9, and assess their consistency. DESIGN: Population-based retrospective cohort. SETTING: Large medical centre between 2013 and 2017. PARTICIPANTS: Adults ≥18 years old with encounters in each of 4 years (2013, 2014, 2016, 2017). MAIN OUTCOME MEASURES: MWI conditions mapped to ICD-10 codes, and additional conditions and codes added to produce a new MWI-ICD10 and updated MWI-ICD9. We compared the prevalence of ICD-coded MWI conditions within the ICD-9 era (2013-2014), within the ICD-10 era (2016-2017) and across the ICD-9-ICD-10 transition in 2015 (washout period) among adults present in both sets of comparison years. We computed the prevalence and change in prevalence of conditions when using MWI-ICD10 versus MWI-ICD9. RESULTS: 88 175 adults met inclusion criteria. Participants were 60.8% female, 50.5% white, with mean age 54.7±17.3 years and baseline MWI-ICD9 4.47±6.02 (range 0-64.33). Of 94 conditions, 65 had <1% difference across the ICD-9-ICD-10 transition and similar minimal changes within ICD coding eras. CONCLUSIONS: MWI-ICD10 captured the prevalence of chronic conditions nearly identically to that of the validated MWI-ICD9, along with notable but explicable changes across the ICD-10 transition. This new comprehensive person-centred index enables quantification of cumulative disease burden and physical functioning in adults as a clinically meaningful measure of multimorbidity in electronic health record and claims data.

Comorbidity Clusters Among Adults With Cerebral Palsy: A Latent Class Analysis.

INTRODUCTION: Adults with cerebral palsy are at risk for early multimorbidity onset, but little is known about the composition of multimorbidity profiles or how these profiles present across adulthood. The objective of this study was to identify multimorbidity profiles and association with mortality among adults with cerebral palsy. METHODS: This retrospective cohort study used a random 20% fee-for-service Medicare database from January 1, 2008 to December 31, 2019 from adults aged ≥18 years with cerebral palsy. Latent class analyses using 4-class models were conducted within each age cohort (young adults aged 18-39 years, middle adulthood aged 40-64 years, and older adults aged ≥65 years) to determine patterns of 30 comorbidities defined using the International Classification of Diseases, Ninth Revision codes, identified from January 1, 2008 to December 31, 2010, and their association with mortality through December 31, 2019 (up to 11 years of follow-up); statistical analysis was performed in 2023. RESULTS: Three classes were relatively consistent in the composition of comorbidities across young (n=7,020), middle (n=13,554), and older (n=4,193) cohorts: (1) low morbidity (low proportion of all comorbidities) representing 50.1% (young), 41.4% (middle), and 30.9% (older) of the cohorts; (2) neurologic multimorbidity (e.g., epilepsy, intellectual disabilities) representing 26.0% (young), 26.6% (middle), and 14.7% (older) of the cohorts; and complex multimorbidity (e.g., cardiorespiratory, nutritional, musculoskeletal, neurologic) representing 26.0% (young), 26.6% (middle), and 14.7% (older) of the cohorts. The fourth class varied by young (mental health disorders), middle (hypertension), and older (hypertension and osteoarthritis) age cohorts. Compared with the low morbidity class, other classes had an increased mortality rate for each age cohort (hazard ratio range=1.34-5.58, all p<0.001). CONCLUSIONS: Findings provide insight into varied multimorbidity profiles and associations with mortality across the life course for adults with cerebral palsy.

Carotid intima media thickness and cardiometabolic dysfunction: the Study of Women's Health Across the Nation.

OBJECTIVE: Carotid artery intima media thickness (cIMT) and adventitial diameter (AD) are subclinical atherosclerosis indicators. Metabolic syndrome (MetS) and obesity are risk factors for atherosclerosis, but their combined impact on atherosclerosis risk is unknown. This study sought to examine the effect of the co-occurrence of MetS with obesity on cIMT and AD. METHODS: The Study of Women's Health Across the Nation (SWAN) is a multi-center, multi-ethnic study. Carotid ultrasound assessments and concurrent physiologic measurements were undertaken between 2009 and 2013. This cross-sectional analysis included 1,433 women with body mass index ≥18.5 kg/m 2 and free of prevalent clinical cardiovascular disease. Multivariable linear regression models were used to relate maximum cIMT and AD (dependent variables) with obesity, MetS and their interaction. RESULTS: The average age was 60.1 years (standard deviation [SD], 2.7 y). The prevalence of obesity and MetS was 44% and 35%, respectively. Women with obesity had a 0.051 mm larger mean cIMT and women with MetS had a 0.057 mm larger cIMT versus women without the respective conditions (both P < 0.001). There was a statistically significant interaction between obesity and MetS ( P = 0.011); women with both had a model-adjusted predicted mean cIMT of 0.955 mm (95% confidence interval [CI], 0.897-1.013), higher than those with MetS alone (0.946 mm; 95% CI, 0.887-1.005), obesity alone (0.930 mm; 95% CI, 0.873-0.988), or neither condition (0.878 mm; 95% CI, 0.821-0.935). AD results were similar. CONCLUSIONS: Early detection and treatment of atherosclerotic changes may prevent significant disease. This study suggests there is a minimal impact of obesity on carotid artery thickness beyond MetS alone. All individuals with metabolic dysfunction, regardless of obesity status, should be considered at increased risk for atherosclerotic changes.

Disease Severity of Respiratory Syncytial Virus Compared with COVID-19 and Influenza Among Hospitalized Adults Aged ≥60 Years - IVY Network, 20 U.S. States, February 2022-May 2023.

On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended respiratory syncytial virus (RSV) vaccination for adults aged ≥60 years, offered to individual adults using shared clinical decision-making. Informed use of these vaccines requires an understanding of RSV disease severity. To characterize RSV-associated severity, 5,784 adults aged ≥60 years hospitalized with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 U.S. states during February 1, 2022-May 31, 2023. Multivariable logistic regression was used to compare RSV disease severity with COVID-19 and influenza severity on the basis of the following outcomes: 1) standard flow (<30 L/minute) oxygen therapy, 2) high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV), 3) intensive care unit (ICU) admission, and 4) invasive mechanical ventilation (IMV) or death. Overall, 304 (5.3%) enrolled adults were hospitalized with RSV, 4,734 (81.8%) with COVID-19 and 746 (12.9%) with influenza. Patients hospitalized with RSV were more likely to receive standard flow oxygen, HFNC or NIV, and ICU admission than were those hospitalized with COVID-19 or influenza. Patients hospitalized with RSV were more likely to receive IMV or die compared with patients hospitalized with influenza (adjusted odds ratio = 2.08; 95% CI = 1.33-3.26). Among hospitalized older adults, RSV was less common, but was associated with more severe disease than COVID-19 or influenza. High disease severity in older adults hospitalized with RSV is important to consider in shared clinical decision-making regarding RSV vaccination.

Use of neuromuscular blockade for neck dissection and association with iatrogenic nerve injury.

BACKGROUND: Cranial nerve injury is an uncommon but significant complication of neck dissection. We examined the association between the use of intraoperative neuromuscular blockade and iatrogenic cranial nerve injury during neck dissection. METHODS: This was a single-center, retrospective, electronic health record review. Study inclusion criteria stipulated patients > 18 years who had ≥ 2 neck lymphatic levels dissected for malignancy under general anesthesia with a surgery date between 2008 - 2018. Use of neuromuscular blockade during neck dissection was the primary independent variable. This was defined as any use of rocuronium, cisatracurium, or vecuronium upon anesthesia induction without reversal with sugammadex prior to surgical incision. Univariate tests were used to compare variables between those patients with, and those without, iatrogenic cranial nerve injury. Multivariable logistic regression determined predictors of cranial nerve injury and was performed incorporating Firth's estimation given low prevalence of the primary outcome. RESULTS: Our cohort consisted of 925 distinct neck dissections performed in 897 patients. Neuromuscular blockade was used during 285 (30.8%) neck dissections. Fourteen instances (1.5% of surgical cases) of nerve injury were identified. On univariate logistic regression, use of neuromuscular blockade was not associated with iatrogenic cranial nerve injury (OR: 1.73, 95% CI: 0.62 - 4.86, p = 0.30). There remained no significant association on multivariable logistic regression controlling for patient age, sex, weight, ASA class, paralytic dose, history of diabetes, stroke, coronary artery disease, carotid atherosclerosis, myocardial infarction, and cardiac arrythmia (OR: 1.87, 95% CI: 0.63 - 5.51, p = 0.26). CONCLUSIONS: In this study, use of neuromuscular blockade intraoperatively during neck dissection was not associated with increased rates of iatrogenic cranial nerve injury. While this investigation provides early support for safe use of neuromuscular blockade during neck dissection, future investigation with greater power remains necessary.

Longitudinal Patterns of Postfracture Outpatient Physical Therapy and Occupational Therapy Use and Its Association With 3-Year Mortality Among Adults With Cerebral Palsy.

OBJECTIVE: Fragility fractures are common among adults with cerebral palsy (CP), but clinical rehabilitation use after fracture and its effect on long-term health outcomes have not been sufficiently studied. The objectives of this study were to identify patterns of the use of physical therapy, occupational therapy, or both in the 6-month postfracture period and the association with 3-year mortality in adults with CP. METHODS: This retrospective cohort study included adults who were ≥18 years old, had CP, and had sustained an incident fragility fracture between January 1, 2014, and December 31, 2016, as identified from a random 20% Medicare fee-for-service dataset. Six-month outpatient physical therapy or occupational therapy use patterns after fracture were identified using group-based trajectory modeling. Cox regression determined the association between physical therapy or occupational therapy use trajectory patterns and mortality from 6 months to 3 years after fracture, adjusting for confounders. Effect modification by key characteristics was tested, including age, sex, and the modified Whitney Comorbidity Index (mWCI), which is a CP-specific comorbidity index that better captures overall medical complexity. RESULTS: Of the 2429 participants included, the majority (73.2%) were characterized as having little to no probability of physical therapy or occupational therapy use, whereas 16.0 and 10.7% were characterized as having early initiation and later initiation, respectively. Compared to the mortality rate for the little to no physical therapy or occupational therapy group, the mortality rates were 26% lower for the early physical therapy or occupational therapy initiation group (hazard ratio [HR] = 0.74; 95% CI = 0.55-1.00) and were 20% lower for the later initiation group (HR = 0.80; 95% CI = 0.57-1.12). There was effect modification by the mWCI. The mortality rate was lower when the early initiation and later initiation groups were compared to the little to no initiation group across all mWCI values examined (median and interquartile range), but the effect was stronger (ie, lower mortality rate) for lower mWCI values for both early initiation and later initiation groups. CONCLUSION: Most adults with CP underutilize outpatient physical therapy or occupational therapy services within 6 months postfracture. Early or later initiation versus little to no physical therapy or occupational therapy use was associated with a lower HR of mortality, although the effect was stronger and statistically significant among those with less medical complexity. IMPACT: Throughout their lives, the use of rehabilitation services in individuals with CP, including physical therapy and occupational therapy, dramatically declines despite the need for continued rehabilitation across their lifespans. This study characterized longitudinal physical therapy or occupational therapy use patterns in the 6 months following a fragility fracture among adults with CP and found that nearly 3 in 4 adults with CP had little to no physical therapy or occupational therapy use during this critical window to optimize postfracture health and function. Further, those who more regularly used physical therapy or occupational therapy services, regardless of the timing of initiation (early vs later), had significantly improved survival up to 3 years after fracture, suggesting the need for greater access to and delivery of clinical rehabilitation services.

Electroencephalographic Biomarkers, Cerebral Oximetry, and Postoperative Cognitive Function in Adult Noncardiac Surgical Patients: A Prospective Cohort Study.

BACKGROUND: Perioperative neurocognitive disorders are a major public health issue, although there are no validated neurophysiologic biomarkers that predict cognitive function after surgery. This study tested the hypothesis that preoperative posterior electroencephalographic alpha power, alpha frontal-parietal connectivity, and cerebral oximetry would each correlate with postoperative neurocognitive function. METHODS: This was a single-center, prospective, observational study of adult (older than 18 yr) male and female noncardiac surgery patients. Whole-scalp, 16-channel electroencephalography and cerebral oximetry were recorded in the preoperative, intraoperative, and immediate postoperative settings. The primary outcome was the mean postoperative T-score of three National Institutes of Health Toolbox Cognition tests-Flanker Inhibitory Control and Attention, List Sorting Working Memory, and Pattern Comparison Processing Speed. These tests were obtained at preoperative baseline and on the first two postoperative mornings. The lowest average score from the first two postoperative days was used for the primary analysis. Delirium was a secondary outcome (via 3-min Confusion Assessment Method) measured in the postanesthesia care unit and twice daily for the first 3 postoperative days. Last, patient-reported outcomes related to cognition and overall well-being were collected 3 months postdischarge. RESULTS: Sixty-four participants were recruited with a median (interquartile range) age of 59 (48 to 66) yr. After adjustment for baseline cognitive function scores, no significant partial correlation (ρ) was detected between postoperative cognition scores and preoperative relative posterior alpha power (%; ρ = -0.03, P = 0.854), alpha frontal-parietal connectivity (via weight phase lag index; ρ = -0.10, P = 0.570, respectively), or preoperative cerebral oximetry (%; ρ = 0.21, P = 0.246). Only intraoperative frontal-parietal theta connectivity was associated with postoperative delirium (F[1,6,291] = 4.53, P = 0.034). No electroencephalographic or oximetry biomarkers were associated with cognitive or functional outcomes 3 months postdischarge. CONCLUSIONS: Preoperative posterior alpha power, frontal-parietal connectivity, and cerebral oximetry were not associated with cognitive function after noncardiac surgery.

Cardiometabolic disease and obesity patterns differentially predict acute kidney injury after total joint replacement: a retrospective analysis.

BACKGROUND: Acute kidney injury (AKI) is a frequent yet understudied postoperative total joint arthroplasty complication. This study aimed to describe cardiometabolic disease co-occurrence using latent class analysis, and associated postoperative AKI risk. METHODS: This retrospective analysis examined patients ≥18 years old undergoing primary total knee or hip arthroplasties within the US Multicenter Perioperative Outcomes Group of hospitals from 2008 to 2019. AKI was defined using modified Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Latent classes were constructed from eight cardiometabolic diseases including hypertension, diabetes, and coronary artery disease, excluding obesity. A mixed-effects logistic regression model was constructed for the outcome of any AKI and the exposure of interaction between latent class and obesity status adjusting for preoperative and intraoperative covariates. RESULTS: Of 81 639 cases, 4007 (4.9%) developed AKI. Patients with AKI were more commonly older and non-Hispanic Black, with more significant comorbidity. A latent class model selected three groups of cardiometabolic patterning, labelled 'hypertension only' (n=37 223), 'metabolic syndrome (MetS)' (n=36 503), and 'MetS+cardiovascular disease (CVD)' (n=7913). After adjustment, latent class/obesity interaction groups had differential risk of AKI compared with those in 'hypertension only'/non-obese. Those 'hypertension only'/obese had 1.7-fold increased odds of AKI (95% confidence interval [CI]: 1.5-2.0). Compared with 'hypertension only'/non-obese, those 'MetS+CVD'/obese had the highest odds of AKI (odds ratio 3.1, 95% CI: 2.6-3.7), whereas 'MetS+CVD'/non-obese had 2.2 times the odds of AKI (95% CI: 1.8-2.7; model area under the curve 0.76). CONCLUSIONS: The risk of postoperative AKI varies widely between patients. The current study suggests that the co-occurrence of metabolic conditions (diabetes mellitus, hypertension), with or without obesity, is a more important risk factor for acute kidney injury than individual comorbid diseases.

Racial Disparity in Residual Sleep Apnea After Adenotonsillectomy.

OBJECTIVE: Black children have a higher risk of residual obstructive sleep apnea after adenotonsillectomy than non-Black children. We analyzed Childhood Adenotonsillectomy Trial data to better understand this disparity. We hypothesized that (1) child-level factors, such as asthma, smoke exposure, obesity, sleep duration, and (2) socioeconomic factors, such as maternal education, maternal health, and neighborhood disadvantage, may confound, modify, or mediate the association between Black race and residual obstructive sleep apnea after adenotonsillectomy. STUDY DESIGN: Secondary analysis of a randomized controlled trial. SETTING: Seven tertiary care centers. METHODS: We included two hundred and twenty-four 5-to-9-year-olds with mild-to-moderate obstructive sleep apnea who underwent adenotonsillectomy. The outcome was residual obstructive sleep apnea 6 months after surgery. Data were analyzed with logistic regression and mediation analysis. RESULTS: Of 224 included children, 54% were Black. Compared with non-Black children, Black children had 2.7 times greater odds of residual sleep apnea (95% confidence interval [CI]: 1.2, 6.1; p = .01), adjusted for age, sex, and baseline Apnea Hypopnea Index. There was significant effect modification by obesity. Among obese children, there was no association between Black race and outcome. However, nonobese Black children were 4.9 times as likely to have residual sleep apnea than non-Black children (95% CI: 1.2, 20.0; p < 0.01). There was no significant mediation by any of the child-level or socioeconomic factors tested. CONCLUSION: There was substantial effect modification by obesity on the association between Black race and residual sleep apnea after adenotonsillectomy for mild-to-moderate sleep apnea. Black race was associated with poorer outcome among nonobese but not obese children.

K-medoids clustering of hospital admission characteristics to classify severity of influenza virus infection.

Background: Patients are admitted to the hospital for respiratory illness at different stages of their disease course. It is important to appropriately analyse this heterogeneity in surveillance data to accurately measure disease severity among those hospitalized. The purpose of this study was to determine if unique baseline clusters of influenza patients exist and to examine the association between cluster membership and in-hospital outcomes. Methods: Patients hospitalized with influenza at two hospitals in Southeast Michigan during the 2017/2018 (n = 242) and 2018/2019 (n = 115) influenza seasons were included. Physiologic and laboratory variables were collected for the first 24 h of the hospital stay. K-medoids clustering was used to determine groups of individuals based on these values. Multivariable linear regression or Firth's logistic regression were used to examine the association between cluster membership and clinical outcomes. Results: Three clusters were selected for 2017/2018, mainly differentiated by blood glucose level. After adjustment, those in C171 had 5.6 times the odds of mechanical ventilator use than those in C172 (95% CI: 1.49, 21.1) and a significantly longer mean hospital length of stay than those in both C172 (mean 1.5 days longer, 95% CI: 0.2, 2.7) and C173 (mean 1.4 days longer, 95% CI: 0.3, 2.5). Similar results were seen between the two clusters selected for 2018/2019. Conclusion: In this study of hospitalized influenza patients, we show that distinct clusters with higher disease acuity can be identified and could be targeted for evaluations of vaccine and influenza antiviral effectiveness against disease attenuation. The association of higher disease acuity with glucose level merits evaluation.

Preoperative Predictors of Severe Respiratory Events After Tonsillectomy: Consideration for Pediatric Intensive Care Admission.

OBJECTIVE: Few data are available to guide postadenotonsillectomy (AT) pediatric intensive care (PICU) admission. The aim of this study of children with a preoperative polysomnogram (PSG) was to assess whether preoperative information may predict severe respiratory events (SRE) after AT. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary center. METHODS: Children aged 6 months to 17 years who underwent AT with preoperative polysomnography (2012-2018) were identified by billing codes. Data were extracted from medical records. SRE were defined as any 1 or more of desaturations <80% requiring intervention; newly initiated positive airway pressure; postoperative intubation; pneumonia/pneumonitis; respiratory code, cardiac arrest, or death. We hypothesized that SRE would be associated with age <24 months, major medical comorbidity, obesity (>95th percentile), apnea-hypopnea index (AHI) ≥ 30, and O2 nadir <70% on PSG. Analysis was performed with multivariable logistic regression. RESULTS: Of 1774 subjects, 28 (1.7%) experienced SRE. Compared to those without, children with SRE were on average younger (3 vs 5 years, p < .01) with a greater probability of medical comorbidities (59% vs 18%, p < .001). After adjustment for sex, black race, obesity, and age <24 months, children with major medical comorbidity were more likely than other children to have SRE (odds ratio [OR]: 14.2; 95% confidence interval [CI]: [5.7, 35.2]), as were children with AHI ≥ 30 (OR: 7.7 [3.0, 19.9]), or O2 nadir <70% (OR 6.1 [2.1, 17.9]). Age, obesity, sex, and black race did not independently predict SRE. CONCLUSION: PICU admission may be most prudent for children with complex medical co-morbidities, high AHI (>30), and/or low O2 nadir (<70%).

The Association of Inflammatory Factors With Peripheral Neuropathy: The Study of Women's Health Across the Nation.

PURPOSE: Previous work has focused on the role of diabetes in peripheral neuropathy (PN), but PN often occurs before, and independently from, diabetes. This study measures the association of cardiometabolic and inflammatory factor with PN, independent of diabetes. METHODS: Study of Women's Health Across the Nation participants (n = 1910), ages 60 to 73 (mean 65.6) were assessed for PN by symptom questionnaire and monofilament testing at the 15th follow-up visit (V15). Anthropometric measures and biomarkers were measured at study baseline approximately 20 years prior, and C-reactive protein (CRP) and fibrinogen were measured longitudinally. Log-binomial regression was used to model the association between metabolic syndrome (MetS), obesity (≥35 body mass index), CRP, and fibrinogen with PN, adjusting for sociodemographic and health behavior measures. RESULTS: Baseline MetS [prevalence ratio (PR) 1.79, 95% CI (1.45, 2.20)], obesity [PR 2.08 (1.65, 2.61)], median CRP [PR 1.32 per log(mg/dL), (1.20, 1.45)], and mean fibrinogen (PR 1.28 per 100 mg/dL, (1.09, 1.50)] were associated with PN symptoms at V15. After excluding participants with baseline diabetes or obesity, MetS [PR 1.59 (1.17, 2.14)] and CRP [PR 1.19 per log(mg/dL), (1.06, 1.35)] remained statistically significantly associated with PN. There was a negative interaction between MetS and obesity, and the association between these conditions and PN was mediated by CRP. CONCLUSIONS: Cardiometabolic factors and inflammation are significantly associated with PN, independent of diabetes and obesity. CRP mediates the relationship of both obesity and MetS with PN, suggesting an etiological role of inflammation in PN in this sample.

Five-year risk of fracture and subsequent fractures among adults with cerebral palsy.

Background: Epidemiologic evidence documenting the incidence of fracture and subsequent fractures among adults with cerebral palsy (CP) is lacking, which could inform fracture prevention efforts. The objective was to characterize the 5-year rate of initial and subsequent fragility fractures among adults with CP. Methods: This retrospective cohort study used Medicare claims from 01/01/2008-12/31/2019 from adults ≥18 years old with CP (n = 44,239) and elderly ≥65 years old without CP (n = 2,176,463) as a comparison. The incidence rate (IR), IR ratio (IRR), and site distribution were estimated for the initial and subsequent fragility fractures over 5-years by sex and age. Results: The IR of fragility fracture at any site over the 5-year follow-up was similar for 18-30-year-old men with CP (IR = 5.2; 95%CI = 4.4-5.9) and 30-34-year-old women with CP (IR = 6.3; 95%CI = 5.3-7.2) compared to the same sex youngest-old (65-74 years old) without CP (IRR = 1.09 and 0.94, respectively, both P > 0.05), and increased with older age for those with CP. The number of fragility fractures and IR of subsequent fragility fractures was similar for young men and middle-aged women with CP compared to elderly without CP, and increased with older age for those with CP. The proportion of fragility fracture at the tibia/fibula decreased while the vertebral column and multiple simultaneous sites (most involved hip/lower extremities) increased with older age. Conclusion: Young and middle-aged adults with CP had similar-to-worse initial and subsequent fragility fracture profiles compared to the general elderly population- a well characterized group for bone fragility. Findings emphasize the need for fracture prevention efforts at younger ages for CP, possibly by ~5 decades younger.

Carbon Dioxide, Blood Pressure, and Perioperative Stroke: A Retrospective Case-Control Study.

BACKGROUND: The relationship between intraoperative physiology and postoperative stroke is incompletely understood. Preliminary data suggest that either hypo- or hypercapnia coupled with reduced cerebrovascular inflow (e.g., due to hypotension) can lead to ischemia. This study tested the hypothesis that the combination of intraoperative hypotension and either hypo- or hypercarbia is associated with postoperative ischemic stroke. METHODS: We conducted a retrospective, case-control study via the Multicenter Perioperative Outcomes Group. Noncardiac, nonintracranial, and nonmajor vascular surgical cases (18 yr or older) were extracted from five major academic centers between January 2004 and December 2015. Ischemic stroke cases were identified via manual chart review and matched to controls (1:4). Time and reduction below key mean arterial blood pressure thresholds (less than 55 mmHg, less than 60 mmHg, less than 65 mmHg) and outside of specific end-tidal carbon dioxide thresholds (30 mmHg or less, 35 mmHg or less, 45 mmHg or greater) were calculated based on total area under the curve. The association between stroke and total area under the curve values was then tested while adjusting for relevant confounders. RESULTS: In total, 1,244,881 cases were analyzed. Among the cases that screened positive for stroke (n = 1,702), 126 were confirmed and successfully matched with 500 corresponding controls. Total area under the curve was significantly associated with stroke for all thresholds tested, with the strongest combination observed with mean arterial pressure less than 55 mmHg (adjusted odds ratio per 10 mmHg-min, 1.17 [95% CI, 1.10 to 1.23], P < 0.0001) and end-tidal carbon dioxide 45 mmHg or greater (adjusted odds ratio per 10 mmHg-min, 1.11 [95% CI, 1.10 to 1.11], P < 0.0001). There was no interaction effect observed between blood pressure and carbon dioxide. CONCLUSIONS: Intraoperative hypotension and carbon dioxide dysregulation may each independently increase postoperative stroke risk.