Genetic and Congenital Anomalies in Infants With Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Infants with hypoxic ischemic encephalopathy (HIE) may have underlying conditions predisposing them to hypoxic-ischemic injury during labor and delivery. It is unclear how genetic and congenital anomalies impact outcomes of HIE. METHODS: Infants with HIE enrolled in a phase III trial underwent genetic testing when clinically indicated. Infants with known genetic or congenital anomalies were excluded. The primary outcome, i.e., death or neurodevelopmental impairment (NDI), was determined at age two years by a standardized neurological examination, Bayley Scales of Infant Development, Third Edition (BSID-III), and the Gross Motor Function Classification Scales. Secondary outcomes included cerebral palsy and BSID-III motor, cognitive, and language scores at age two years. RESULTS: Of 500 infants with HIE, 24 (5%, 95% confidence interval 3% to 7%) were diagnosed with a genetic (n = 15) or congenital (n = 14) anomaly. Infants with and without genetic or congenital anomalies had similar rates of severe encephalopathy and findings on brain magnetic resonance imaging. However, infants with genetic or congenital anomalies were more likely to have death or NDI (75% vs 50%, P = 0.02). Among survivors, those with a genetic or congenital anomaly were more likely to be diagnosed with cerebral palsy (32% vs 13%, P = 0.02), and had lower BSID-III scores in all three domains than HIE survivors without such anomalies. CONCLUSIONS: Among infants with HIE, 5% were diagnosed with a genetic or congenital anomaly. Despite similar clinical markers of HIE severity, infants with HIE and a genetic or congenital anomaly had worse neurodevelopmental outcomes than infants with HIE alone.

Study Protocol for the Social Interventions for Support During Treatment for Endometrial Cancer and Recurrence (SISTER) study: a community engaged national randomized trial.

Aim: Social isolation in cancer patients is correlated with prognosis and is a potential mediator of treatment completion. Black women with endometrial cancer (EC) are at increased risk for social isolation when compared with White patients. We developed the Social Interventions for Support during Treatment for Endometrial Cancer and Recurrence (SISTER) study to compare and evaluate interventions to address social isolation among Black women with high-risk EC in USA. The primary objective of the SISTER study is to determine whether virtual support interventions improve treatment completion compared with Enhanced Usual Care. Secondary objectives include comparing effectiveness virtual evidence-based interventions and evaluating barriers and facilitators to social support delivery. Patients & methods: This is a multi-site prospective, open-label, community-engaged randomized controlled trial, consisting of three intervention arms: enhanced usual care, facilitated support group and one-to-one peer support. Primary outcome will be measured using relative dose. Qualitative semi-structured interviews will be conducted with a subset of participants to contextualize the relative degree or lack thereof of social isolation, over time. Data analysis: Primary analysis will be based on an intent-to-treat analysis. Multivariable analysis will be performed to determine the effect of the intervention on the primary and secondary outcomes of interest, relative dose and social isolation score. Semi-structured interviews will be qualitatively analyzed using inductive and deductive approaches of content analysis. Discussion/conclusion: Endometrial cancer mortality disproportionately affects Black women, and social isolation contributes to this disparity. The SISTER study aims to identify whether and to what extent differing social support vehicles improve key outcomes for Black women in the United States with high-risk EC. Clinical Trial Registration: NCT04930159 (ClinicalTrials.gov).

Artificial Intelligence in Anesthetic Care: A Survey of Physician Anesthesiologists.

BACKGROUND: This study explored physician anesthesiologists' knowledge, exposure, and perceptions of artificial intelligence (AI) and their associations with attitudes and expectations regarding its use in clinical practice. The findings highlight the importance of understanding anesthesiologists' perspectives for the successful integration of AI into anesthesiology, as AI has the potential to revolutionize the field. METHODS: A cross-sectional survey of 27,056 US physician anesthesiologists was conducted to assess their knowledge, perceptions, and expectations regarding the use of AI in clinical practice. The primary outcome measured was attitude toward the use of AI in clinical practice, with scores of 4 or 5 on a 5-point Likert scale indicating positive attitudes. The anticipated impact of AI on various aspects of professional work was measured using a 3-point Likert scale. Logistic regression was used to explore the relationship between participant responses and attitudes toward the use of AI in clinical practice. RESULTS: A 2021 survey of 27,056 US physician anesthesiologists received 1086 responses (4% response rate). Most respondents were male (71%), active clinicians (93%) under 45 (34%). A majority of anesthesiologists (61%) had some knowledge of AI and 48% had a positive attitude toward using AI in clinical practice. While most respondents believed that AI can improve health care efficiency (79%), timeliness (75%), and effectiveness (69%), they are concerned that its integration in anesthesiology could lead to a decreased demand for anesthesiologists (45%) and decreased earnings (45%). Within a decade, respondents expected AI would outperform them in predicting adverse perioperative events (83%), formulating pain management plans (67%), and conducting airway exams (45%). The absence of algorithmic transparency (60%), an ambiguous environment regarding malpractice (47%), and the possibility of medical errors (47%) were cited as significant barriers to the use of AI in clinical practice. Respondents indicated that their motivation to use AI in clinical practice stemmed from its potential to enhance patient outcomes (81%), lower health care expenditures (54%), reduce bias (55%), and boost productivity (53%). Variables associated with positive attitudes toward AI use in clinical practice included male gender (odds ratio [OR], 1.7; P < .001), 20+ years of experience (OR, 1.8; P < .01), higher AI knowledge (OR, 2.3; P = .01), and greater AI openness (OR, 10.6; P < .01). Anxiety about future earnings was associated with negative attitudes toward AI use in clinical practice (OR, 0.54; P < .01). CONCLUSIONS: Understanding anesthesiologists' perspectives on AI is essential for the effective integration of AI into anesthesiology, as AI has the potential to revolutionize the field.

Brain Injury Outcomes after Adjuvant Erythropoietin Neuroprotection for Moderate or Severe Neonatal Hypoxic-Ischemic Encephalopathy: A Report from the HEAL Trial.

INTRODUCTION: Erythropoietin (Epo) is a putative neuroprotective therapy that did not improve overall outcomes in a phase 3 randomized controlled trial for neonates with moderate or severe hypoxic-ischemic encephalopathy (HIE). However, HIE is a heterogeneous disorder, and it remains to be determined whether Epo had beneficial effects on a subset of perinatal brain injuries. METHODS: This study was a secondary analysis of neuroimaging data from the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Trial, which was conducted from 2016 - 2021 at 17 sites involving 23 US academic medical centers. Participants were neonates >36 weeks' gestation undergoing therapeutic hypothermia for moderate or severe HIE who received 5 doses of study drug (Epoetin alpha 1000 U/kg/dose) or placebo in the first week of life. Treatment assignment was stratified by trial site and severity of encephalopathy. The primary outcome was the locus, pattern and acuity of brain injury as determined by three independent readers using a validated HIE Magnetic Resonance Imaging (MRI) scoring system. RESULTS: Of the 500 infants enrolled in HEAL, 470 (94%) had high quality MRI data obtained at a median of 4.9 days of age (IQR 4.5 - 5.8). The incidence of injury to the deep grey nuclei, cortex, white matter, brainstem and cerebellum was similar between Epo and placebo groups. Likewise, the distribution of injury patterns was similar between groups. Among infants imaged at less than 8 days (n=414), 94 (23%) evidenced only acute, 93 (22%) only subacute and 89 (21%) both acute and subacute injuries, with similar distribution across treatment groups. CONCLUSION: Adjuvant erythropoietin did not reduce the incidence of regional brain injury. Subacute brain injury was more common than previously reported, which has key implications for the development of adjuvant neuroprotective therapies for this population.

Trial Participation and Outcomes Among English-Speaking and Spanish-Speaking Patients With Appendicitis Randomized to Antibiotics: A Secondary Analysis of the CODA Randomized Clinical Trial.

Importance: Spanish-speaking participants are underrepresented in clinical trials, limiting study generalizability and contributing to ongoing health inequity. The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial intentionally included Spanish-speaking participants. Objective: To describe trial participation and compare clinical and patient-reported outcomes among Spanish-speaking and English-speaking participants with acute appendicitis randomized to antibiotics. Design, Setting, and Participants: This study is a secondary analysis of the CODA trial, a pragmatic randomized trial comparing antibiotic therapy with appendectomy in adult patients with imaging-confirmed appendicitis enrolled at 25 centers across the US from May 1, 2016, to February 28, 2020. The trial was conducted in English and Spanish. All 776 participants randomized to antibiotics are included in this analysis. The data were analyzed from November 15, 2021, through August 24, 2022. Intervention: Randomization to a 10-day course of antibiotics or appendectomy. Main Outcomes and Measures: Trial participation, European Quality of Life-5 Dimensions (EQ-5D) questionnaire scores (higher scores indicating a better health status), rate of appendectomy, treatment satisfaction, decisional regret, and days of work missed. Outcomes are also reported for a subset of participants that were recruited from the 5 sites with a large proportion of Spanish-speaking participants. Results: Among eligible patients 476 of 1050 Spanish speakers (45%) and 1076 of 3982 of English speakers (27%) consented, comprising the 1552 participants who underwent 1:1 randomization (mean age, 38.0 years; 976 male [63%]). Of the 776 participants randomized to antibiotics, 238 were Spanish speaking (31%). Among Spanish speakers randomized to antibiotics, the rate of appendectomy was 22% (95% CI, 17%-28%) at 30 days and 45% (95% CI, 38%-52%) at 1 year, while in English speakers, these rates were 20% (95% CI, 16%-23%) at 30 days and 42% (95% CI 38%-47%) at 1 year. Mean EQ-5D scores were 0.93 (95% CI, 0.92-0.95) among Spanish speakers and 0.92 (95% CI, 0.91-0.93) among English speakers. Symptom resolution at 30 days was reported by 68% (95% CI, 61%-74%) of Spanish speakers and 69% (95% CI, 64%-73%) of English speakers. Spanish speakers missed 6.69 (95% CI, 5.51-7.87) days of work on average, while English speakers missed 3.76 (95% CI, 3.20-4.32) days. Presentation to the emergency department or urgent care, hospitalization, treatment dissatisfaction, and decisional regret were low for both groups. Conclusions and Relevance: A high proportion of Spanish speakers participated in the CODA trial. Clinical and most patient-reported outcomes were similar for English- and Spanish-speaking participants treated with antibiotics. Spanish speakers reported more days of missed work. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

How well does neonatal neuroimaging correlate with neurodevelopmental outcomes in infants with hypoxic-ischemic encephalopathy?

BACKGROUND: In newborns with hypoxic-ischemic encephalopathy (HIE), the correlation between neonatal neuroimaging and the degree of neurodevelopmental impairment (NDI) is unclear. METHODS: Infants with HIE enrolled in a randomized controlled trial underwent neonatal MRI/MR spectroscopy (MRS) using a harmonized protocol at 4-6 days of age. The severity of brain injury was measured with a validated scoring system. Using proportional odds regression, we calculated adjusted odds ratios (aOR) for the associations between MRI/MRS measures of injury and primary ordinal outcome (i.e., normal, mild NDI, moderate NDI, severe NDI, or death) at age 2 years. RESULTS: Of 451 infants with MRI/MRS at a median age of 5 days (IQR 4.5-5.8), outcomes were normal (51%); mild (12%), moderate (14%), severe NDI (13%); or death (9%). MRI injury score (aOR 1.06, 95% CI 1.05, 1.07), severe brain injury (aOR 39.6, 95% CI 16.4, 95.6), and MRS lactate/n-acetylaspartate (NAA) ratio (aOR 1.6, 95% CI 1.4,1.8) were associated with worse primary outcomes. Infants with mild/moderate MRI brain injury had similar BSID-III cognitive, language, and motor scores as infants with no injury. CONCLUSION: In the absence of severe injury, brain MRI/MRS does not accurately discriminate the degree of NDI. Given diagnostic uncertainty, families need to be counseled regarding a range of possible neurodevelopmental outcomes. IMPACT: Half of all infants with hypoxic-ischemic encephalopathy (HIE) enrolled in a large clinical trial either died or had neurodevelopmental impairment at age 2 years despite receiving therapeutic hypothermia. Severe brain injury and a global pattern of brain injury on MRI were both strongly associated with death or neurodevelopmental impairment. Infants with mild or moderate brain injury had similar mean BSID-III cognitive, language, and motor scores as infants with no brain injury on MRI. Given the prognostic uncertainty of brain MRI among infants with less severe degrees of brain injury, families should be counseled regarding a range of possible neurodevelopmental outcomes.

Iron supplementation and the risk of bronchopulmonary dysplasia in extremely low gestational age newborns.

BACKGROUND: The aim of this study was to determine the relationship between iron exposure and the development of bronchopulmonary dysplasia (BPD). METHODS: A secondary analysis of the PENUT Trial dataset was conducted. The primary outcome was BPD at 36 weeks gestational age and primary exposures of interest were cumulative iron exposures in the first 28 days and through 36 weeks' gestation. Descriptive statistics were calculated for study cohort characteristics with analysis adjusted for the factors used to stratify randomization. RESULTS: Of the 941 patients, 821 (87.2%) survived to BPD evaluation at 36 weeks, with 332 (40.4%) diagnosed with BPD. The median cohort gestational age was 26 weeks and birth weight 810 g. In the first 28 days, 76% of infants received enteral iron and 55% parenteral iron. The median supplemental cumulative enteral and parenteral iron intakes at 28 days were 58.5 and 3.1 mg/kg, respectively, and through 36 weeks' 235.8 and 3.56 mg/kg, respectively. We found lower volume of red blood cell transfusions in the first 28 days after birth and higher enteral iron exposure in the first 28 days after birth to be associated with lower rates of BPD. CONCLUSIONS: We find no support for an increased risk of BPD with iron supplementation. TRIAL REGISTRATION NUMBER: NCT01378273. https://clinicaltrials.gov/ct2/show/NCT01378273 IMPACT: Prior studies and biologic plausibility raise the possibility that iron administration could contribute to the pathophysiology of oxidant-induced lung injury and thus bronchopulmonary dysplasia in preterm infants. For 24-27-week premature infants, this study finds no association between total cumulative enteral iron supplementation at either 28-day or 36-week postmenstrual age and the risk for developing bronchopulmonary dysplasia.

Perception of Treatment Success and Impact on Function with Antibiotics or Appendectomy for Appendicitis: A Randomized Clinical Trial with an Observational Cohort.

OBJECTIVE: To compare secondary patient reported outcomes of perceptions of treatment success and function for patients treated for appendicitis with appendectomy vs. antibiotics at 30 days. SUMMARY BACKGROUND DATA: The Comparison of Outcomes of antibiotic Drugs and Appendectomy trial found antibiotics noninferior to appendectomy based on 30-day health status. To address questions about outcomes among participants with lower socioeconomic status, we explored the relationship of sociodemographic and clinical factors and outcomes. METHODS: We focused on 4 patient reported outcomes at 30 days: high decisional regret, dissatisfaction with treatment, problems performing usual activities, and missing >10 days of work. The randomized (RCT) and observational cohorts were pooled for exploration of baseline factors. The RCT cohort alone was used for comparison of treatments. Logistic regression was used to assess associations. RESULTS: The pooled cohort contained 2062 participants; 1552 from the RCT. Overall, regret and dissatisfaction were low whereas problems with usual activities and prolonged missed work occurred more frequently. In the RCT, those assigned to antibiotics had more regret (Odd ratios (OR) 2.97, 95% Confidence intervals (CI) 2.05-4.31) and dissatisfaction (OR 1.98, 95%CI 1.25-3.12), and reported less missed work (OR 0.39, 95%CI 0.27-0.56). Factors associated with function outcomes included sociodemographic and clinical variables for both treatment arms. Fewer factors were associated with dissatisfaction and regret. CONCLUSIONS: Overall, participants reported high satisfaction, low regret, and were frequently able to resume usual activities and return to work. When comparing treatments for appendicitis, no single measure defines success or failure for all people. The reported data may inform discussions regarding the most appropriate treatment for individuals. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02800785.

Patient and Nodule Characteristics Associated With a Lung Cancer Diagnosis Among Individuals With Incidentally Detected Lung Nodules.

BACKGROUND: Pulmonary nodules are a common incidental finding on CT imaging. Few studies have described patient and nodule characteristics associated with a lung cancer diagnosis using a population-based cohort. RESEARCH QUESTION: Does a relationship exist between patient and nodule characteristics and lung cancer among individuals with incidentally detected pulmonary nodules, and can this information be used to create exploratory lung cancer prediction models with reasonable performance characteristics? STUDY DESIGN AND METHODS: We conducted a retrospective cohort study of adults older than 18 years with lung nodules of any size incidentally detected by chest CT imaging between 2005 and 2015. All patients had at least 2 years of complete follow-up. To evaluate the relationship between patient and nodule characteristics and lung cancer, we used binomial regression. We used logistic regression to create prediction models, and we internally validated model performance using bootstrap optimism correction. RESULTS: Among 7,240 patients with a median age of 67 years, 56% of whom were women, with a median BMI of 28 kg/m2, 56% of whom were ever smokers, 31% of whom had prior nonlung malignancy, with a median nodule size 5.6 mm, 57% of whom had multiple nodules, and 40% of whom had an upper lobe nodule, 265 patients (3.7%; 95% CI, 3.2%-4.1%) had a diagnosis of lung cancer. In a multivariate analysis, age, sex, BMI, smoking history, and nodule size and location were associated with a lung cancer diagnosis, whereas prior malignancy and nodule number and laterality were not. We were able to construct two prediction models with an area under the curve value of 0.75 (95% CI, 0.72-0.80) and reasonable calibration. INTERPRETATION: Lung cancer is uncommon among individuals with incidentally detected lung nodules. Some, but not all, previously identified factors associated with lung cancer also were associated with this outcome in this sample. These findings may have implications for clinical practice, future practice guidelines, and the development of novel lung cancer prediction models for individuals with incidentally detected lung nodules.

Association of Patient Belief About Success of Antibiotics for Appendicitis and Outcomes: A Secondary Analysis of the CODA Randomized Clinical Trial.

Importance: A patient's belief in the likely success of a treatment may influence outcomes, but this has been understudied in surgical trials. Objective: To examine the association between patients' baseline beliefs about the likelihood of treatment success with outcomes of antibiotics for appendicitis in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial. Design, Setting, and Participants: This was a secondary analysis of the CODA randomized clinical trial. Participants from 25 US medical centers were enrolled between May 3, 2016, and February 5, 2020. Included in the analysis were participants with appendicitis who were randomly assigned to receive antibiotics in the CODA trial. After informed consent but before randomization, participants who were assigned to receive antibiotics responded to a baseline survey including a question about how successful they believed antibiotics could be in treating their appendicitis. Interventions: Participants were categorized based on baseline survey responses into 1 of 3 belief groups: unsuccessful/unsure, intermediate, and completely successful. Main Outcomes and Measures: Three outcomes were assigned at 30 days: (1) appendectomy, (2) high decisional regret or dissatisfaction with treatment, and (3) persistent signs and symptoms (abdominal pain, tenderness, fever, or chills). Outcomes were compared across groups using adjusted risk differences (aRDs), with propensity score adjustment for sociodemographic and clinical factors. Results: Of the 776 study participants who were assigned antibiotic treatment in CODA, a total of 425 (mean [SD] age, 38.5 [13.6] years; 277 male [65%]) completed the baseline belief survey before knowing their treatment assignment. Baseline beliefs were as follows: 22% of participants (92 of 415) had an unsuccessful/unsure response, 51% (212 of 415) had an intermediate response, and 27% (111 of 415) had a completely successful response. Compared with the unsuccessful/unsure group, those who believed antibiotics could be completely successful had a 13-percentage point lower risk of appendectomy (aRD, -13.49; 95% CI, -24.57 to -2.40). The aRD between those with intermediate vs unsuccessful/unsure beliefs was -5.68 (95% CI, -16.57 to 5.20). Compared with the unsuccessful/unsure group, those with intermediate beliefs had a lower risk of persistent signs and symptoms (aRD, -15.72; 95% CI, -29.71 to -1.72), with directionally similar results for the completely successful group (aRD, -15.14; 95% CI, -30.56 to 0.28). Conclusions and Relevance: Positive patient beliefs about the likely success of antibiotics for appendicitis were associated with a lower risk of appendectomy and with resolution of signs and symptoms by 30 days. Pathways relating beliefs to outcomes and the potential modifiability of beliefs to improve outcomes merit further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Fleischner Society Guideline Recommendations for Incidentally Detected Pulmonary Nodules and the Probability of Lung Cancer.

PURPOSE: The Fleischner Society aims to limit further evaluations of incidentally detected pulmonary nodules when the probability of lung cancer is <1% and to pursue further evaluations when the probability of lung cancer is ≥1%. To evaluate the internal consistency of guideline goals and recommendations, the authors evaluated stratum-specific recommendations and 2-year probabilities of lung cancer. METHODS: A retrospective cohort study (2005-2015) was conducted of individuals enrolled in one of two integrated health systems with solid nodules incidentally detected on CT. The 2017 Fleischner Society guidelines were used to define strata on the basis of smoking status and nodule size and number. Lung cancer diagnoses within 2 years of nodule detection were ascertained using cancer registry data. Confidence interval (CI) inspection was used to determine if stratum-specific probabilities of lung cancer were different than 1%. RESULTS: Among 5,444 individuals with incidentally detected lung nodules (median age, 66 years; 54% women; 57% smoked; median nodule size, 5.5 mm; 55% with multiple nodules), 214 (3.9%; 95% CI, 3.4%-4.5%) were diagnosed with lung cancer within 2 years. For 7 of 12 strata (58%), 2,765 patients (51%), and 194 lung cancer cases (91%), there was alignment between Fleischner Society goals and recommendations. Alignment was indeterminate for 5 strata (42%), 2,679 patients (49%), and 20 lung cancer cases (9%) because CIs for the probability of lung cancer spanned 1%. CONCLUSIONS: Fleischner Society guideline goals and recommendations align at least half the time. It is uncertain whether alignment of guideline goals and recommendations occurs more often.

Analysis of Outcomes Associated With Outpatient Management of Nonoperatively Treated Patients With Appendicitis.

Importance: In the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which found antibiotics to be noninferior, approximately half of participants randomized to receive antibiotics had outpatient management with hospital discharge within 24 hours. If outpatient management is safe, it could increase convenience and decrease health care use and costs. Objective: To assess the use and safety of outpatient management of acute appendicitis. Design, Setting, and Participants: This cohort study, which is a secondary analysis of the CODA trial, included 776 adults with imaging-confirmed appendicitis who received antibiotics at 25 US hospitals from May 1, 2016, to February 28, 2020. Exposures: Participants randomized to antibiotics (intravenous then oral) could be discharged from the emergency department based on clinician judgment and prespecified criteria (hemodynamically stable, afebrile, oral intake tolerated, pain controlled, and follow-up confirmed). Outpatient management and hospitalization were defined as discharge within or after 24 hours, respectively. Main Outcomes and Measures: Outcomes compared among patients receiving outpatient vs inpatient care included serious adverse events (SAEs), appendectomies, health care encounters, satisfaction, missed workdays at 7 days, and EuroQol 5-dimension (EQ-5D) score at 30 days. In addition, appendectomy incidence among outpatients and inpatients, unadjusted and adjusted for illness severity, was compared. Results: Among 776 antibiotic-randomized participants, 42 (5.4%) underwent appendectomy within 24 hours and 8 (1.0%) did not receive their first antibiotic dose within 24 hours, leaving 726 (93.6%) comprising the study population (median age, 36 years; range, 18-86 years; 462 [63.6%] male; 437 [60.2%] White). Of these participants, 335 (46.1%; site range, 0-89.2%) were discharged within 24 hours, and 391 (53.9%) were discharged after 24 hours. Over 7 days, SAEs occurred in 0.9 (95% CI, 0.2-2.6) per 100 outpatients and 1.3 (95% CI, 0.4-2.9) per 100 inpatients; in the appendicolith subgroup, SAEs occurred in 2.3 (95% CI, 0.3-8.2) per 100 outpatients vs 2.8 (95% CI, 0.6-7.9) per 100 inpatients. During this period, appendectomy occurred in 9.9% (95% CI, 6.9%-13.7%) of outpatients and 14.1% (95% CI, 10.8%-18.0%) of inpatients; adjusted analysis demonstrated a similar difference in incidence (-4.0 percentage points; 95% CI, -8.7 to 0.6). At 30 days, appendectomies occurred in 12.6% (95% CI, 9.1%-16.7%) of outpatients and 19.0% (95% CI, 15.1%-23.4%) of inpatients. Outpatients missed fewer workdays (2.6 days; 95% CI, 2.3-2.9 days) than did inpatients (3.8 days; 95% CI, 3.4-4.3 days) and had similar frequency of return health care visits and high satisfaction and EQ-5D scores. Conclusions and Relevance: These findings support that outpatient antibiotic management is safe for selected adults with acute appendicitis, with no greater risk of complications or appendectomy than hospital care, and should be included in shared decision-making discussions of patient preferences for outcomes associated with nonoperative and operative care. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Self-selection vs Randomized Assignment of Treatment for Appendicitis.

Importance: For adults with appendicitis, several randomized clinical trials have demonstrated that antibiotics are an effective alternative to appendectomy. However, it remains unknown how the characteristics of patients in such trials compare with those of patients who select their treatment and whether outcomes differ. Objective: To compare participants in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) randomized clinical trial (RCT) with a parallel cohort study of participants who declined randomization and self-selected treatment. Design, Setting, and Participants: The CODA trial was conducted in 25 US medical centers. Participants were enrolled between May 3, 2016, and February 5, 2020; all participants were eligible for at least 1 year of follow-up, with all follow-up ending in 2021. The randomized cohort included 1094 adults with appendicitis; the self-selection cohort included patients who declined participation in the randomized group, of whom 253 selected appendectomy and 257 selected antibiotics. In this secondary analysis, characteristics and outcomes in both self-selection and randomized cohorts are described with an exploratory analysis of cohort status and receipt of appendectomy. Interventions: Appendectomy vs antibiotics. Main Outcomes and Measures: Characteristics among participants randomized to either appendectomy or antibiotics were compared with those of participants who selected their own treatment. Results: Clinical characteristics were similar across the self-selection cohort (510 patients; mean age, 35.8 years [95% CI, 34.5-37.1]; 218 female [43%; 95% CI, 39%-47%]) and the randomized group (1094 patients; mean age, 38.2 years [95% CI, 37.4-39.0]; 386 female [35%; 95% CI, 33%-38%]). Compared with the randomized group, those in the self-selection cohort were less often Spanish speaking (n = 99 [19%; 95% CI, 16%-23%] vs n = 336 [31%; 95% CI, 28%-34%]), reported more formal education (some college or more, n = 355 [72%; 95% CI, 68%-76%] vs n = 674 [63%; 95% CI, 60%-65%]), and more often had commercial insurance (n = 259 [53%; 95% CI, 48%-57%] vs n = 486 [45%; 95% CI, 42%-48%]). Most outcomes were similar between the self-selection and randomized cohorts. The number of patients undergoing appendectomy by 30 days was 38 (15.3%; 95% CI, 10.7%-19.7%) among those selecting antibiotics and 155 (19.2%; 95% CI, 15.9%-22.5%) in those who were randomized to antibiotics (difference, 3.9%; 95% CI, -1.7% to 9.5%). Differences in the rate of appendectomy were primarily observed in the non-appendicolith subgroup. Conclusions and Relevance: This secondary analysis of the CODA RCT found substantially similar outcomes across the randomized and self-selection cohorts, suggesting that the randomized trial results are generalizable to the community at large. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Patient Factors Associated With Appendectomy Within 30 Days of Initiating Antibiotic Treatment for Appendicitis.

IMPORTANCE: Use of antibiotics for the treatment of appendicitis is safe and has been found to be noninferior to appendectomy based on self-reported health status at 30 days. Identifying patient characteristics associated with a greater likelihood of appendectomy within 30 days in those who initiate antibiotics could support more individualized decision-making. OBJECTIVE: To assess patient factors associated with undergoing appendectomy within 30 days of initiating antibiotics for appendicitis. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study using data from the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) randomized clinical trial, characteristics among patients who initiated antibiotics were compared between those who did and did not undergo appendectomy within 30 days. The study was conducted at 25 US medical centers; participants were enrolled between May 3, 2016, and February 5, 2020. A total of 1552 participants with acute appendicitis were randomized to antibiotics (776 participants) or appendectomy (776 participants). Data were analyzed from September 2020 to July 2021. EXPOSURES: Appendectomy vs antibiotics. MAIN OUTCOMES AND MEASURES: Conditional logistic regression models were fit to estimate associations between specific patient factors and the odds of undergoing appendectomy within 30 days after initiating antibiotics. A sensitivity analysis was performed excluding participants who underwent appendectomy within 30 days for nonclinical reasons. RESULTS: Of 776 participants initiating antibiotics (mean [SD] age, 38.3 [13.4] years; 286 [37%] women and 490 [63%] men), 735 participants had 30-day outcomes, including 154 participants (21%) who underwent appendectomy within 30 days. After adjustment for other factors, female sex (odds ratio [OR], 1.53; 95% CI, 1.01-2.31), radiographic finding of wider appendiceal diameter (OR per 1-mm increase, 1.09; 95% CI, 1.00-1.18), and presence of appendicolith (OR, 1.99; 95% CI, 1.28-3.10) were associated with increased odds of undergoing appendectomy within 30 days. Characteristics that are often associated with increased risk of complications (eg, advanced age, comorbid conditions) and those clinicians often use to describe appendicitis severity (eg, fever: OR, 1.28; 95% CI, 0.82-1.98) were not associated with odds of 30-day appendectomy. The sensitivity analysis limited to appendectomies performed for clinical reasons provided similar results regarding appendicolith (adjusted OR, 2.41; 95% CI, 1.49-3.91). CONCLUSIONS AND RELEVANCE: This cohort study found that presence of an appendicolith was associated with a nearly 2-fold increased risk of undergoing appendectomy within 30 days of initiating antibiotics. Clinical characteristics often used to describe severity of appendicitis were not associated with odds of 30-day appendectomy. This information may help guide more individualized decision-making for people with appendicitis.

Cancer and Pregnancy: National Trends.

OBJECTIVE: Cancer and pregnancy are likely increasing; however, updated estimates are needed to optimally address the unique needs of this patient population. The study aims to estimate the prevalence of cancer and cancer survivorship at delivery, to test the change in odds of cancer and cancer survivorship at delivery over the 10-year period, and to compare medical conditions, serious events, and obstetric complications between pregnancies with and without cancer at delivery. STUDY DESIGN: We conducted a retrospective analysis of the National Inpatient Sample (NIS), the largest all-payer inpatient health database in the United States. We identified delivery admissions from 2004 to 2013 with a concurrent diagnosis of cancer using International Classification of Disease, ninth revision (ICD-9) codes. Multivariable logistic regression was used to test the change in prevalence of concurrent cancer, cancer survivorship, and pregnancy and to compare outcomes between deliveries with and without cancer. All analyses were adjusted for NIS-provided population weights and strata. RESULTS: During the study period, the NIS represented a national estimate of 40,855,208 deliveries. The odds of cancer increased from 3.41/10,000 deliveries in 2004 to 4.33/10,000 in 2013. This trend was statistically significant, including after adjustment for maternal age (adjusted odds ratio [aOR] = 1.03 [95% confidence interval (CI): 1.01-1.04]). Cancer survivorship at delivery increased significantly (aOR = 1.07 [95% CI: 1.06-1.08]). Women with cancer more often experienced one or more of the following: death, ventilation, cardiac arrest, sepsis, or acute respiratory or renal failure during delivery (aOR for composite outcome 10.7 [95% CI: 6.6-17.2]), even after adjustment in a multivariable logistic regression model. CONCLUSION: The odds of cancer and cancer survivorship at delivery increased from 2004 to 2013, independent of maternal age. Women with cancer were more likely to experience medical or obstetric complications during their delivery compared with women without cancer. These findings highlight the importance of obstetric and oncologic clinical and research collaboration to improve patient care. KEY POINTS: · The odds of cancer at delivery increased.. · Women with cancer may have delivery complications.. · Cancer survivorship at delivery increased..