Predictors of Disease Activity in Patients With Juvenile Idiopathic Arthritis at 12 and 24 Months After Diagnosis.

OBJECTIVE: Identification of characteristics associated with active disease in juvenile idiopathic arthritis (JIA) could inform early disease treatment strategies. This study evaluated characteristics associated with active disease at 12 and 24 months after JIA diagnosis in the era in which biologic disease-modifying antirheumatic drugs (DMARDs) became available for JIA. METHODS: This single-center retrospective study from 2004 through 2018 assessed characteristics associated with active nonsystemic categories of JIA at 12 and 24 months after diagnosis. Relative prevalence (RP) of disease activity was evaluated in relation to prespecified characteristics. Using RP, the effect of increasing biologic DMARD availability on these predictors was assessed at 12 months. RESULTS: A total of 1,151 patients with JIA were included. At 12 months, a 40% to 45% higher point prevalence of active disease was noted in older children (>5 years). Patients with active disease at 3 months had a greater prevalence of active disease at 12 months (RP 1.5, 95% confidence interval [CI] 1.2-1.8) and 24 months (RP 1.3, 95% CI 1-1.6). Compared to oligoarticular JIA, polyarticular RF-negative, psoriatic, and enthesitis-related JIA had a greater prevalence of active disease at 12 and 24 months. At 24 months, a greater prevalence of active disease was observed in children ≥10 years. RP of active disease was 25% lower in the late cohort (2013-2018) than in the earliest cohort (2004-2008; RP 0.75, 95% CI 0.62-0.92) when more biologic medications were available, but disease activity predictors were broadly similar over time. CONCLUSION: Patients with JIA with active disease at 12 and 24 months were older at diagnosis, categorized as polyarticular RF-negative, psoriatic, or enthesitis-related JIA. Active disease at 3 months after diagnosis was associated with worse outcomes at 12 and 24 months.

Colorectal Cancer Screening After Sequential Outreach Components in a Demographically Diverse Cohort.

Importance: Organized screening outreach can reduce differences in colorectal cancer (CRC) incidence and mortality between demographic subgroups. Outcomes associated with additional outreach, beyond universal outreach, are not well known. Objective: To compare CRC screening completion by race and ethnicity, age, and sex after universal automated outreach and additional personalized outreach. Design, Setting, and Participants: This observational cohort study included screening-eligible individuals aged 50 to 75 years assessed during 2019 in a community-based organized CRC screening program within the Kaiser Permanente Northern California (KPNC) integrated health care delivery setting. For KPNC members who are not up to date with screening by colonoscopy, each year the program first uses automated outreach (mailed prescreening notification postcards and fecal immunochemical test [FIT] kits, automated telephone calls, and postcard reminders), followed by personalized components for nonresponders (telephone calls, electronic messaging, and screening offers during office visits). Data analyses were performed between November 2021 and February 2023 and completed on February 5, 2023. Exposures: Completed CRC screening via colonoscopy, sigmoidoscopy, or FIT. Main Outcomes and Measures: The primary outcome was the proportion of participants completing an FIT or colonoscopy after each component of the screening process. Differences across subgroups were assessed using the χ2 test. Results: This study included 1 046 745 KPNC members. Their mean (SD) age was 61.1 (6.9) years, and more than half (53.2%) were women. A total of 0.4% of members were American Indian or Alaska Native, 18.5% were Asian, 7.2% were Black, 16.2% were Hispanic, 0.8% were Native Hawaiian or Other Pacific Islander, and 56.5% were White. Automated outreach significantly increased screening participation by 31.1%, 38.1%, 29.5%, 31.9%, 31.8%, and 34.5% among these groups, respectively; follow-up personalized outreach further significantly increased participation by absolute additional increases of 12.5%, 12.4%, 13.3%, 14.4%, 14.7%, and 11.2%, respectively (all differences P < .05 compared with White members). Overall screening coverage at the end of the yearly program differed significantly among members who were American Indian or Alaska Native (74.1%), Asian (83.5%), Black (77.7%), Hispanic (76.4%), or Native Hawaiian or Other Pacific Islander (74.4%) compared with White members (82.2%) (all differences P < .05 compared with White members). Screening completion was similar by sex; older members were substantially more likely to be up to date with CRC screening both before and at the end of the screening process. Conclusions and Relevance: In this cohort study of a CRC screening program, sequential automated and personalized strategies each contributed to substantial increases in screening completion in all demographic groups. These findings suggest that such programs may potentially reduce differences in CRC screening completion across demographic groups.

Randomized trials of multicancer screening tests: augmenting their ability to identify a genuine mortality benefit.

Randomized trials of the efficacy of multicancer early detection, by means of measurement of cell-free DNA and/or protein biomarkers in peripheral blood specimens, will attempt to document a difference in cancer mortality between persons assigned to intervention and control arms. Their ability to do so is limited by the relatively low rate of death from individual forms of cancer, the relatively low sensitivity of the tests currently being used, and the use of other cancer screening modalities among trial participants. However, if those same blood specimens also could be obtained from control arm participants in a given trial and then tested for the same markers, with results not known (or not made available) until the conclusion of follow-up for cancer mortality, it would be possible to compare mortality from given forms of cancer between test-positive individuals whose results were known and not known during the course of the trial. Such an analysis addresses the impact of a stimulus to offer targeted diagnostic testing, potentially leading to early treatment, against cancer mortality. Among persons who screen as positive, it should provide a relatively more sensitive means of gauging a possible mortality benefit resulting from multicancer screening.

Effectiveness of Endoscopic Screening on Esophageal Cancer Incidence and Mortality: A 9-Year Report of the Endoscopic Screening for Esophageal Cancer in China (ESECC) Randomized Trial.

PURPOSE: To evaluate the effectiveness of endoscopic screening against incidence of and mortality from esophageal squamous cell carcinoma (ESCC). METHODS: From January 2012 to September 2016, we conducted a community-based cluster randomized controlled trial involving permanent residents age 45-69 years in a high-risk region for ESCC in northern China. A total of 668 targeted villages were randomly assigned in a 1:1 ratio to the screening group (offered Lugol's chromoendoscopy) or control group (no screening). Intention-to-treat and per-protocol analyses were performed to compare esophageal cancer (EC) incidence and mortality between the two groups. The per-protocol analysis adjusted for nonadherence to the screening procedure. RESULTS: A total of 33,847 participants were included in the analysis: 17,104 in the screening group, 15,165 (88.7%) of whom underwent screening, and 16,743 in the control group. During a maximum follow-up of 9 years, EC incidence in the screening and control groups were 60.9 and 72.5 per 100,000 person-years, respectively; mortality in the screening and control groups were 29.7 and 32.4 per 100,000 person-years, respectively. Compared with the control group, the incidence and mortality of the screening group reduced by 19% (adjusted hazard ratio [aHR], 0.81 [95% CI, 0.60 to 1.09]) and 18% (aHR, 0.82 [95% CI, 0.53 to 1.26]), respectively, in the intention-to-treat analysis; and by 22% (aHR, 0.78 [95% CI, 0.56 to 1.10]) and 21% (aHR, 0.79 [95% CI, 0.49 to 1.30]), respectively, in the per-protocol analysis. CONCLUSION: With a 9-year follow-up, our trial suggests that chromoendoscopic screening induces modest reductions in EC incidence and mortality. A more efficient strategy for EC screening and subsequent patient management should be established to guarantee the effectiveness of endoscopic screening.

Factors Associated with Costly Hospital Care among Patients with Dementia and Acute Respiratory Failure.

Rationale: Understanding contributors to costly and potentially burdensome care for patients with dementia is of interest to healthcare systems and may facilitate efforts to promote goal-concordant care. Objective: To identify risk factors, in particular whether an early goals-of-care discussion (GOCD) took place, for high-cost hospitalization among patients with dementia and acute respiratory failure. Methods: We conducted an electronic health record-based retrospective cohort study of 298 adults with dementia hospitalized with respiratory failure (receiving ⩾48 h of mechanical ventilation) within an academic healthcare system. We collected demographic and clinical characteristics, including clinical markers of advanced dementia (weight loss, pressure ulcers, hypernatremia, mobility limitations) and intensive care unit (ICU) service (medical, surgical, neurologic). We ascertained whether a GOCD was documented within 48 hours of ICU admission. We used logistic regression to identify patient characteristics associated with high-cost hospitalization measured using the hospital system accounting database and defined as total cost in the top third of the sample (⩾$145,000). We examined a path model that included hospital length of stay as a final mediator between exposure variables and high-cost hospitalization. Results: Patients in the sample had a median age of 71 (IQR, 62-79) years. Approximately half (49%) were admitted to a medical ICU, 29% to a surgical ICU, and 22% to a neurologic ICU. More than half (59%) had a clinical indicator of advanced dementia. A minority (31%) had a GOCD documented within 48 hours of ICU admission; those who did had a 50% lower risk of a high-cost hospitalization (risk ratio, 0.50; 95% confidence interval, 0.2-0.8). Older age, limited English proficiency, and nursing home residence were associated with a lower likelihood of high-cost hospitalization, whereas greater comorbidity burden and admission to a surgical or neurologic ICU compared with a medical ICU were associated with a higher likelihood of high-cost hospitalization. Conclusions: Early GOCDs for patients with dementia and respiratory failure may promote high-value care by ensuring aggressive and costly life support interventions are aligned with patients' goals. Future work should focus on increasing early palliative care delivery for patients with dementia and respiratory failure, in particular in surgical and neurologic ICU settings.

Risk of Colorectal Cancer and Colorectal Cancer Mortality Beginning One Year after a Negative Fecal Occult Blood Test, among Screen-Eligible 76- to 85-Year-Olds.

BACKGROUND: Colorectal cancer screening is universally recommended for adults ages 45 to 75 years. Noninvasive fecal occult blood tests are effective screening tests recommended by guidelines. However, empirical evidence to inform older adults' decisions about whether to continue screening is sparse, especially for individuals with prior screening. METHODS: This study used a retrospective cohort of older adults at three Kaiser Permanente integrated healthcare systems (Northern California, Southern California, Washington) and Parkland Health. Beginning 1 year following a negative stool-based screening test, cumulative risks of colorectal cancer incidence, colorectal cancer mortality (accounting for deaths from other causes), and non-colorectal cancer mortality were estimated. RESULTS: Cumulative incidence of colorectal cancer in screen-eligible adults ages 76 to 85 with a negative fecal occult blood test 1 year ago (N = 118,269) was 0.23% [95% confidence interval (CI), 0.20%-0.26%] after 2 years and 1.21% (95% CI, 1.13%-1.30%) after 8 years. Cumulative colorectal cancer mortality was 0.03% (95% CI, 0.02%-0.04%) after 2 years and 0.33% (95% CI, 0.28%-0.39%) after 8 years. Cumulative risk of death from non-colorectal cancer causes was 4.81% (95% CI, 4.68%-4.96%) after 2 years and 28.40% (95% CI, 27.95%-28.85%) after 8 years. CONCLUSIONS: Among 76- to 85-year-olds with a recent negative stool-based test, cumulative colorectal cancer incidence and mortality estimates were low, especially within 2 years; death from other causes was over 100 times more likely than death from colorectal cancer. IMPACT: These findings of low absolute colorectal cancer risk, and comparatively higher risk of death from other causes, can inform decision-making regarding whether and when to continue colorectal cancer screening beyond age 75 among screen-eligible adults.

Short-term Endpoints for Cancer Screening Trials: Does Tumor Subtype Matter?

Multicancer early detection tests are precipitating a reexamination of potential short-term endpoints for cancer screening trials. A reduction in advanced stage incidence is a prime candidate, and stage-shift models that substitute early-stage for late-stage survival have been used to predict mortality reduction due to screening. However, standard stage-shift models often ignore prognostic subtypes, effectively implying that cancers detected early also have an associated subtype shift. To illustrate the differences between mortality predictions from stage-shift models that ignore versus preserve prognostic subtype, we use ovarian cancer partitioned by histologic subtype and prostate cancer partitioned by grade. We infer general conditions under which stage-shift models that preserve prognostic subtype are likely to predict mortality reductions that differ from those that ignore subtype and examine the implications for short-term endpoints based on stage in cancer screening trials.

Association between sociodemographic factors and cholesterol-lowering medication use in U.S. adults post-myocardial infarction.

INTRODUCTION: Cholesterol-lowering medications offer effective secondary prevention after myocardial infarction (MI). Our objective was to evaluate the association between sociodemographic factors and cholesterol-lowering medication use in high-risk adults. METHODS: We conducted an analysis using weighted data from 31,408 participants in the 2017 and 2019 Behavioral Risk Factor Surveillance Systems cross-sectional surveys, who had a self-reported history of MI and high blood cholesterol. The sociodemographic factors evaluated were sex, age, race and ethnicity, annual household income, education level, relationship status, and reported healthcare coverage. We estimated the weighted prevalence of medication use, and weighted prevalence differences (with 95% confidence intervals) across categories, adjusting for sex, age group, healthcare coverage, smoking status, hypertension, and diabetes. RESULTS AND DISCUSSION: Overall, 83% of survey participants with a self-reported history of both MI and high blood cholesterol reported currently using a cholesterol-lowering medication. The prevalence of use was only 61% in those without self-reported healthcare coverage, compared to 85% of those with healthcare coverage (adjusted prevalence difference of -20%; 95% CI: -25% to -14%). Use of cholesterol-lowering medication was relatively low in younger adults and higher in older adults, leveling off after age 65 years. The proportion of Native Hawaiian or Pacific Islanders who were using a cholesterol-lowering medication was relatively low, but otherwise there was little variation by race and ethnicity. Household income, education level, and relationship status were weakly or not associated with medication use. CONCLUSIONS: Knowledge of characteristics of persons who are relatively less likely to be adherent with cholesterol-lowering medications for secondary prevention may be useful to policymakers and healthcare providers involved in the long-term treatment of MI patients. Policy makers might consider a reduced cost prescription coverage for persons without current healthcare coverage who have sustained an MI to reduce future cardiovascular morbidity and mortality.

Risk factors for endometrial cancer in Black women.

PURPOSE: The incidence of endometrial cancer (EC) has been increasing faster among Black women than among other racial/ethnic groups in the United States. Although the mortality rate is nearly twice as high among Black than White women, there is a paucity of literature on risk factors for EC among Black women, particularly regarding menopausal hormone use and severe obesity. METHODS: We pooled questionnaire data on 811 EC cases and 3,124 controls from eight studies with data on self-identified Black women (4 case-control and 4 cohort studies). We analyzed cohort studies as nested case-control studies with up to 4 controls selected per case. We used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We observed a positive association between BMI and EC incidence (Ptrend < 0.0001) The OR comparing BMI ≥ 40 vs. < 25 kg/m2 was 3.92 (95% CI 2.91, 5.27). Abdominal obesity among those with BMI < 30 kg/m2 was not appreciably associated with EC risk (OR 1.21, 95% CI 0.74, 1.99). Associations of reproductive history with EC were similar to those observed in studies of White women. Long-term use of estrogen-only menopausal hormones was associated with an increased risk of EC (≥ 5 years vs. never use: OR 2.08, 95% CI: 1.06, 4.06). CONCLUSIONS: Our results suggest that the associations of established risk factors with EC are similar between Black and White women. Other explanations, such as differences in the prevalence of known risk factors or previously unidentified risk factors likely underlie the recent increases in EC incidence among Black women.

Risk of Colorectal Cancer and Colorectal Cancer Mortality Beginning Ten Years after a Negative Colonoscopy, among Screen-Eligible Adults 76 to 85 Years Old.

BACKGROUND: Few empirical data are available to inform older adults' decisions about whether to screen or continue screening for colorectal cancer based on their prior history of screening, particularly among individuals with a prior negative exam. METHODS: Using a retrospective cohort of older adults receiving healthcare at three Kaiser Permanente integrated healthcare systems in Northern California (KPNC), Southern California (KPSC), and Washington (KPWA), we estimated the cumulative risk of colorectal cancer incidence and mortality among older adults who had a negative colonoscopy 10 years earlier, accounting for death from other causes. RESULTS: Screen-eligible adults ages 76 to 85 years who had a negative colonoscopy 10 years earlier were found to be at a low risk of colorectal cancer diagnosis, with a cumulative incidence of 0.39% [95% CI, 0.31%-0.48%) at 2 years that increased to 1.29% (95% CI, 1.02%-1.61%) at 8 years. Cumulative mortality from colorectal cancer was 0.04% (95% CI, 0.02%-0.08%) at 2 years and 0.46% (95% CI, 0.30%-0.70%) at 8 years. CONCLUSIONS: These low estimates of cumulative colorectal cancer incidence and mortality occurred in the context of much higher risk of death from other causes. IMPACT: Knowledge of these results could bear on older adults' decision to undergo or not undergo further colorectal cancer screening, including choice of modality, should they decide to continue screening. See related commentary by Lieberman, p. 6.

Does Distraction Lower Risk of VPI Compared to Conventional Maxillary Advancement? A Retrospective Cohort Study of Adolescents with Cleft Palate.

OBJECTIVE: To determine whether method of maxillary advancement in adolescents with cleft palate with or without cleft lip (CP ± L) influences post-operative velopharyngeal function. DESIGN: Retrospective cohort. SETTING: Pediatric Tertiary Care Hospital. PARTICIPANTS: One hundred and ninety-nine patients with CP ± L after LeFort I osteotomy for maxillary advancement at our institution between January 2007 and June 2019. INTERVENTIONS: LeFort I osteotomy via distraction osteogenesis (DO) or conventional osteotomy (CO). MAIN OUTCOME MEASURES: Patients who underwent DO or CO were compared for the presence of new velopharyngeal insufficiency (VPI), as measured by perceptual rating by a craniofacial speech-language pathologist.Of the 199 patients who underwent maxillary advancement, 126 were available for analysis. The DO group was younger, male, and had more severe maxillary hypoplasia. Following surgery, 17/41 (41.5%) of the DO group had new VPI, compared to just 23/85 (27.1%) of the CO group. After adjusting for cleft type and predicted maxillary advancement, however, there was not sufficient evidence to reject the null hypothesis of no difference in risk of post-operative VPI between the two surgical groups (prevalence ratio [PR] 1.40, 95% CI 0.68-2.90). Increased prevalence of VPI after DO versus CO was primarily observed among patients with a pre-operative velopharyngeal need ratio < 0.8 (PR = 2.01, 95% CI 0.79-5.10) and patients with normal velopharyngeal function pre-operatively (PR = 2.86, 95% CI 0.96-8.50).Our results suggest an increased rather than decreased risk of VPI following DO relative to CO. This association is primarily seen among those with a smaller velopharyngeal ratio or perceptually normal velopharyngeal function pre-operatively.

Psychiatric Diagnoses in Children With CKD Compared to the General Population.

Rationale & Objective: Children with chronic kidney disease (CKD) are subject to physical and psychosocial challenges, which may confer greater risk of developing psychiatric disorders. We sought to examine key psychiatric diagnoses in children with CKD compared with those in the general pediatric population and assess the correlation between parent-reported diagnosis and self-reported symptoms of depression. Study Design: Cross-sectional. Setting & Participants: Children ages 2-17 years receiving current medical care who participated in the Chronic Kidney Disease in Children Study (CKiD) or the National Survey of Children's Health. Exposure: CKD. Outcomes: Parent-reported diagnoses of depression, anxiety, or attention-deficit and hyperactivity disorder (ADHD). Analytical Approach: Using Poisson regression, we determined the age, sex, and race-adjusted prevalence ratio comparing diagnoses between children with CKD and those in the general population overall and within subgroups of sex, race, maternal education status, and CKD stage. Secondarily, we examined the correlation between depression status using standardized self-reported screening instrument scores and parent-reported diagnosis. Results: Eight hundred seventy-five children with CKD and 72,699 children in the general population were included. Those with CKD had an adjusted prevalence ratio of 1.32 (95% CI, 1.01-1.73) for depression, 0.72 (95% CI, 0.52-0.99) for anxiety, and 1.03 (95% CI, 0.86-1.25) for ADHD. The results were similar across subgroups of CKD stage, sex, race, or maternal education. The correlation between parent-reported diagnosis and instrument-detected depression was weak, r = 0.13 (95% CI, 0.03-0.23). Limitations: Retrospective parent- or self-reported data were used. Conclusions: Children with CKD had a higher prevalence of parent-reported depression, equivalent prevalence of attention-deficit and hyperactivity disorder, and lower prevalence of anxiety diagnoses compared to other children. These findings are inconsistent with results of prior studies and suggest that baseline assessments used in CKiD may have limited utility in describing psychiatric disorders among children with CKD. Improved mental health assessment approaches in pediatric nephrology are needed.

The association of severe pain experienced in the pediatric intensive care unit and postdischarge health-related quality of life: A retrospective cohort study.

BACKGROUND: Pain may be a modifiable risk factor for lower health-related quality of life after pediatric critical illness. AIM: To evaluate the association between severe pain experienced in the (pediatrc intensive care unit) and postdischarge health-related quality of life. METHODS: This was a retrospective cohort study. Children aged 1 month to 18 years admitted to the pediatric intensive care unit and enrolled in the Seattle Children's Hospital Outcomes Assessment Program were included. Pain was assessed every 2 h by bedside nursing staff using a behavioral pain scale or numeric pain scale. A day of severe pain was defined as a pediatric intensive care unit day with ≥25% of pain scores ≥7/10. Baseline (preadmission) and postdischarge (median 6 weeks) health-related quality of life was assessed by the Pediatric Quality of Life Inventory (PedsQL™) or the Stein Jessop Functional Status II-R (FS II-R, for children with developmental disability). The cohort was stratified by diagnosis category (surgical vs. medical), and associations were measured using linear regression models. RESULTS: Among 546 patients, 11.9% experienced ≥1 day of severe pain. In multivariable linear regression, each day of severe pain was independently associated with a lower postdischarge health-related quality of life score by 3.6 points (95% CI -6.3 to -0.9) adjusted for baseline health-related quality of life score, age, baseline cognitive function, days with multi-organ dysfunction, pediatric intensive care unit length of stay, and decline in overall function. This association was stronger among surgical patients than medical patients with each day of severe pain resulting in a lower postdischarge health-related quality of life score by 5.3 points (95% CI -9.6 to -0.9) versus 2.6 points (95% CI -5.8 to 0.6). Surgical patients had lower postdischarge emotional functioning than physical functioning subdomain scores. CONCLUSIONS: Children who experience severe pain in the pediatric intensive care unit have lower postdischarge health-related quality of life adjusting for baseline health-related quality of life, particularly among children who have undergone surgery. Attention to pain management may be important to improve postdischarge health-related quality of life.

Multicancer Early Detection: Learning From the Past to Meet the Future.

Multicancer early detection (MCED) tests may soon be available to screen for many cancers using a single blood test, yet little is known about these tests beyond their diagnostic performance. Taking lessons from the history of cancer early detection, we highlight 3 factors that influence how performance of early detection tests translates into benefit and benefit-harm trade-offs: the ability to readily confirm a cancer signal, the population testing strategy, and the natural histories of the targeted cancers. We explain why critical gaps in our current knowledge about each factor prevent reliably projecting the expected clinical impact of MCED testing at this point in time. Our goal is to communicate how much uncertainty there is about the possible effects of MCED tests on population health so that patients, providers, regulatory agencies, and the public are well informed about what is reasonable to expect from this potentially important technological advance. We also urge the community to invest in a coordinated effort to collect data on MCED test dissemination and outcomes so that these can be tracked and studied while the tests are rigorously evaluated for benefit, harm, and cost.

Hyperoxia after pediatric cardiac arrest: Association with survival and neurological outcomes.

OBJECTIVE: To evaluate the association between hyperoxia in the first 24 hours after in-hospital pediatric cardiac arrest and mortality and poor neurological outcome. METHODS: This is a retrospective cohort study of inpatients in a freestanding children's hospital. We included all patients younger than 18 years of age with in-hospital cardiac arrest between December 2012 and December 2019, who achieved return of circulation (ROC) for longer than 20 minutes, survived at least 24 hours after cardiac arrest, and had documented PaO2 or SpO2 during the first 24 hours after ROC. Hyperoxia was defined as having at least one level of PaO2 above 200 mmHg in the first 24 hours after cardiac arrest. RESULTS: There were 187 patients who met eligibility criteria, of whom 48% had hyperoxia during the first 24 hours after cardiac arrest. In-hospital mortality was 41%, with similar mortality between oxygenation groups (hyperoxia 45% vs no hyperoxia 38%). We did not observe an association between hyperoxia and in-hospital mortality or poor neurological outcome after adjusting for confounders (odds ratio 1.2, 95% confidence interval 0.5-2.8). On sensitivity analysis using two additional cutoffs of PaO2 (>150 mmHg and > 300 mmHg), there was also no association with in-hospital mortality or poor neurological outcome after adjusting for confounders. Similarly, on multivariable logistic regression using SpO2 > 99% as the exposure, there was no difference in the frequency of death or poor neurological outcome at hospital discharge. CONCLUSION: Hyperoxia after pediatric cardiac arrest was common and was not associated with worse in-hospital outcomes.

Association of Antidepressant Continuation in Pregnancy and Infant Birth Weight.

PURPOSE: The aim of the study was to evaluate the association of antidepressant continuation in pregnancy with infant birth weight among women using antidepressants before pregnancy. METHODS: This retrospective cohort study used electronic health data linked with state birth records. We identified singleton live births (2001-2014) to enrolled women with 1 or more antidepressant prescriptions filled 6 months or less before pregnancy, including "continuers" (≥1 antidepressant fills during pregnancy, n = 1775) and "discontinuers" (no fill during pregnancy, n = 1249). We compared birth weight, small or large for gestational age (SGA or LGA), low birth weight (LBW; <2500 g), and macrosomia (>4500 g) between the 2 groups, using inverse probability of treatment weighting to account for pre-pregnancy characteristics, including mental health conditions. RESULTS: After weighting, infants born to antidepressant continuers weighed 71.9 g less than discontinuers' infants (95% confidence interval [CI], -115.5 to -28.3 g), with a larger difference for female infants (-106.4 g; 95% CI, -164.6 to -48.1) than male infants (-48.5 g; 95% CI, -107.2 to 10.3). For female infants, SGA risk was greater in continuers than discontinuers (relative risk [RR],1.54; 95% CI, 1.02 to 2.32). Low birth weight risk was greater in continuers with 50% or more of days covered (RR, 1.69; 95% CI, 1.11 to 2.58) and exposure in the second trimester (RR, 1.53; 95% CI, 1.02 to 2.29), as compared with discontinuers. CONCLUSIONS: Depending on infant sex, as well as duration and timing of use, continuation of antidepressant use during pregnancy may be associated with lower infant birth weight, with corresponding increases in LBW and SGA.

Incidence of Atrial Fibrillation in Persons with Very High Serum Levels of N-Terminal Pro-B-Type Natriuretic Peptide: The Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: While persons in the upper fourth or fifth of the distribution of serum levels of N-terminal pro-B type natriuretic peptide (NT-proBNP) are at a sharply increased risk of developing atrial fibrillation, their absolute risk of this condition (about 20 per 1000 per year) is not clearly high enough to justify prevention or early detection measures. We sought to determine whether the incidence of atrial fibrillation among persons with VERY high levels of NT-proBNP might be sufficiently high to warrant further action. DESIGN AND SETTING: Among persons enrolled in the Multi-Ethnic Study of Atherosclerosis, we documented rates of new onset atrial fibrillation in those with increasingly high serum levels of NT-proBNP. RESULTS: There was a monotonic increase in the incidence of atrial fibrillation with increasing serum level of NT-proBNP, reaching rates of about 50-70 cases per 1000 person-years among those in the upper 3.1% of the distribution (above 422 pg/mL). In this group the incidence tended to be somewhat higher still among persons who were at increased risk of atrial fibrillation for other reasons (eg older age), but in no subgroup did the incidence reach 100 per 1000 person-years. CONCLUSION: Serum levels of NT-proBNP have a considerable ability to predict the development of atrial fibrillation. However, the value of screening middle aged and older adults for these levels hinges largely on the ability of interventions in screen-positive people to lead to a reduced incidence of atrial fibrillation and its complications.

Prognostic Biomarkers for Thrombotic Microangiopathy after Acute Graft-versus-Host Disease: A Nested Case-Control Study.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a complication of allogeneic hematopoietic cell transplantation (HCT) that often occurs following the development of acute graft-versus-host disease (aGVHD). In this study, we aimed to identify early TMA biomarkers among patients with aGVHD. We performed a nested-case-control study from a prospective cohort of allogeneic HCT recipients, matching on the timing and severity of antecedent aGVHD. We identified 13 TMA cases and 25 non-TMA controls from 208 patients in the cohort. Using multivariable conditional logistic regression, the odds ratio for TMA compared with non-TMA was 2.65 (95% confidence interval [CI], 1.00 to 7.04) for every 100 ng/mL increase in terminal complement complex sC5b9 and 2.62 (95% CI, 1.56 to 4.38) for every 1000 pg/mL increase in angiopoietin-2 (ANG2) at the onset of aGVHD. ADAMTS13 and von Willebrand factor (VWF) antigens were not appreciably associated with TMA. Using a Cox regression model incorporating sC5b9 >300 ng/mL and ANG2 >3000 pg/mL at the onset of aGVHD, the adjusted hazard ratio for mortality was 5.33 (95% CI, 1.57 to 18.03) for the high-risk group (both elevated) and 4.40 (95% CI, 1.60 to 12.07) for the intermediate-risk group (one elevated) compared with the low-risk group (neither elevated). In conclusion, we found that elevated sC5b9 and ANG2 levels at the onset of aGVHD were associated with the development of TMA and possibly mortality after accounting for the timing and severity of aGVHD. The results suggest important roles of complement activation and endothelial dysfunction in the pathogenesis of TMA. Measurement of these biomarkers at the onset of aGVHD may inform prognostic enrichment for preventive trials and improve clinical care.