Abstract Disclosure: P.C. White: Consulting Fee; Self; Neurocrine Biosciences, Inc.. Research Investigator; Self; Neurocrine Biosciences, Inc. G.P. Sen: Employee; Self; Neurocrine Biosciences, Inc. F. Tang: Employee; Self; Cytel. J. Chen: Employee; Self; PicnicHealth. K. Lin-Su: Advisory Board Member; Self; CARES Foundation. D. Matos: Employee; Self; CARES Foundation. H. Cheng: Employee; Self; Neurocrine Biosciences, Inc. E. Roberts: Employee; Self; Neurocrine Biosciences, Inc. J.L. Chan: Employee; Self; Neurocrine Biosciences, Inc. G.S. Jeha: Employee; Self; Neurocrine Biosciences, Inc.. Introduction: Patients with congenital adrenal hyperplasia (CAH) are exposed to excess androgens and glucocorticoids (GC), which can affect growth and lead to obesity and other metabolic complications. CAHtalog is an active US-based CAH registry developed in partnership with CARES Foundation on the PicnicHealth platform to abstract retrospective and prospective medical record data. This study reports auxological and comorbidity data for pediatric and adult patients in the CAHtalog registry. Methods: All available medical records for consented adult and pediatric patients were collected. Data were abstracted and structured into a de-identified dataset. CAHtalog data available as of October 2023 were included for analysis. Auxological data were compared to the 2000 CDC growth data. Changes in body mass index (BMI) since the first documented measurements were evaluated. Comorbidities were defined based on diagnosis codes (ICD-9/10), laboratory measurements, vital signs, and/or clinical notes. Results: Data from 32 adult (mean age: 35.8±12.7 years; 72% female) and 35 pediatric patients (mean age: 12.7±5.5 years; 51% female) were available. From the first through last medical record with relevant ages (≥18 or <18 years), median follow-up durations were 13 years (adult) and 11 years (pediatric). Pediatric patients had early growth acceleration (that was more pronounced in females) with 95% confidence intervals for height-for-age of 66-99th percentile for females (2-10 years) and 42-87th percentile for males (2-13 years), followed by blunted pubertal growth. The mean peak bone age to chronological age ratio was 1.2±0.2 at age 7 years. The mean BMI-for-age consistently exceeded the 90th percentile in children aged ≥6 years, particularly for females. In adults, obesity (BMI ≥30) was highly prevalent in both females (74%) and males (33%) at all ages (61% overall), exceeding NHANES 2017-2018 general population prevalence (42%). Hypertension (53%), fatigue (47%), acne (36%), hyperlipidemia (33%), and insomnia/sleep disturbances (28%) were common comorbidities. Conclusion: Our CAH data reveal a persistent abnormal growth pattern, characterized by accelerated growth in early childhood and a deceleration in adolescents; early obesity was noted and sustained into adulthood. The anomalous growth trajectory and high rate of comorbidities reiterate the importance of early intervention and targeted disease management in this population. Presentation: 6/2/2024

This paper studies the relationship between military conflicts and state-building in pre-imperial China. I develop an incomplete contract model to examine rulers' and local administrators' incentives in conflict. Defensive wars drive decentralization: landowning local administrators have more to gain from a successful defense and are therefore more committed to it. Offensive wars drive centralization: the landowning ruler has personnel control over the non-landowning local administrator and can therefore force the latter to participate in less lucrative attacks. Model predictions are corroborated with empirical evidence and historical case studies, and offer broader implications for the political divergence between China and Europe.

BACKGROUND:The 2018 anatomic physiologic (AP) classification American Heart Association/American College of Cardiology (AHA/ACC) Guidelines for Adults with Congenital Heart Disease (ACHD) encompasses both native and post-operative anatomy and physiology to guide care management. As some physiologic conditions and post-operative states lack specific International Classification of Diseases (ICD) 9- Clinical Modification (CM) and 10-CM codes, an ICD code-based classification approximating the ACHD AP classification is needed for population-based studies. METHODS:A total of 232 individuals, aged ≥ 18 years at the time of a health encounter between January 1, 2010 and December 31, 2019 and identified with at least one of 87 ICD codes for a congenital heart defect were validated through medical chart review. Individuals were assigned one of 4 mutually exclusive modified AP classification categories: (1) severe AB, (2) severe CD, (3) non-severe AB, or (4) non-severe CD, based on native anatomy "severe" or "non-severe" and physiology AB ("none" or "mild") or CD ("moderate" or "severe") by two methods: (1) medical record review, and (2) ICD and Current Procedural Terminology (CPT) code-based classification. The composite outcome was defined as a combination of a death, emergency department (ED) visits, or any hospitalizations that occurred at least 6 months after the index date and was assessed by each modified AP classification method. RESULTS:Of 232 cases (52.2% male, 71.1% White), 28.4% experienced a composite outcome a median of 1.6 years after the index encounter. No difference in prediction of the composite outcome was seen based on modified AP classification between chart review and ICD code-based methodology. CONCLUSION:Modified AP classification by chart review and ICD codes are comparable in predicting the composite outcome at least 6 months after classification. Modified AP classification using ICD code-based classification of CHD native anatomy and physiology is an important tool for population-based ACHD surveillance using administrative data.

How to soften resistance to state-building efforts by reform losers? This paper highlights a strategy of compensation via the bureaucracy, in which the ruler offers meaningful government offices in exchange for elites’ acceptance of state-building reforms. We empirically explore this strategy in the context of the Northern Wei Dynasty (386 - 534 AD), which terminated an era of state weakness in early medieval China that initially resulted from entrenched landowning interests and fragile barbarian kingdoms. Our unique dataset combines geocoded family background and career histories of around 2,600 elites with information on medieval Chinese strongholds, which we use to infer state weakness. Leveraging a comprehensive state-building reform in the late 5\textsuperscript{th} century, difference-in-differences estimates document that the reform led to a sustained, substantial increase in the total number of powerful aristocrats from localities with strongholds recruited into the imperial bureaucracy. Subsequent estimates provide evidence for three mechanisms through which compensation facilitates state-building. First, offices taken by these elites came with direct benefits of power and prestige. Second, by transforming these aristocrats from local powerfuls into national stakeholders, these offices potentially induced the realignment of their interests toward those of the dynasty. Third, bureaucracy provided the regime with institutional tools of power-sharing to mitigate credible commitment problems. Findings in this paper shed light on the causes of the ``First Great Divergence,’’ where similar barbarian invasions at similar times led to political fragmentation in Europe but further state consolidation in China.

BACKGROUND:Culture of bronchoalveolar lavage (BAL) specimens takes time to report. We tested whether a molecular diagnostic test could accelerate donor lung assessment and treatment.METHODS:We compared BioFire Film Array Pneumonia Panel (BFPP) with standard of care (SOC) tests on lung allograft samples at three time points: (1) donor BAL at organ recovery, (2) donor bronchial tissue and airway swab at implantation, and (3) first recipient BAL following lung implantation. Primary outcomes were the difference in time to result (Wilcoxon signed-ranked tests) and the agreement in results between BFPP and SOC assays (Gwet's agreement coefficient).RESULTS:We enrolled 50 subjects. In donor lung BAL specimens, BFPP detected 52 infections (14 out of 26 pathogens in the panel). Viral and bacterial BFPP results were reported 2.4 h (interquartile range, IQR 2.0-6.4) following BAL versus 4.6 h (IQR 1.9-6.0, p = 0.625) for OPO BAL viral SOC results and 66 h (IQR 47-87, p < .0001) for OPO BAL bacterial SOC results. Although there was high overall agreement of results between BAL-BFPP versus OPO BAL-SOC tests (Gwet's AC p < .001 for all), the level of agreement differed among 26 pathogens designed in BFPP and differed by types of specimens. BFPP could not detect many infections identified by SOC assays.CONCLUSIONS:BFPP decreased time to detection of lung pathogens among donated lungs, but it cannot replace SOC tests due to the limited number of pathogens in the panel.

BackgroundAdministrative data permit analysis of large cohorts but rely on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes that may not reflect true congenital heart defects (CHDs). Methods and ResultsCHDs in 1497 cases with at least 1 encounter between January 1, 2010 and December 31, 2019 in 2 health care systems, identified by at least 1 of 87 ICD-9-CM/ICD-10-CM CHD codes were validated through medical record review for the presence of CHD and CHD native anatomy. Interobserver and intraobserver reliability averaged >95%. Positive predictive value (PPV) of ICD-9-CM/ICD-10-CM codes for CHD was 68.1% (1020/1497) overall, 94.6% (123/130) for cases identified in both health care systems, 95.8% (249/260) for severe codes, 52.6% (370/703) for shunt codes, 75.9% (243/320) for valve codes, 73.5% (119/162) for shunt and valve codes, and 75.0% (39/52) for "other CHD" (7 ICD-9-CM/ICD-10-CM codes). PPV for cases with >1 unique CHD code was 85.4% (503/589) versus 56.3% (498/884) for 1 CHD code. Of cases with secundum atrial septal defect ICD-9-CM/ICD-10-CM codes 745.5/Q21.1 in isolation, PPV was 30.9% (123/398). Patent foramen ovale was present in 66.2% (316/477) of false positives. True positives had younger mean age at first encounter with a CHD code than false positives (22.4 versus 26.3 years; P=0.0017). ConclusionsCHD ICD-9-CM/ICD-10-CM codes have modest PPV and may not represent true CHD cases. PPV was improved by selecting certain features, but most true cases did not have these characteristics. The development of algorithms to improve accuracy may improve accuracy of electronic health records for CHD surveillance.

Background: The 2018 Adult Congenital Heart Disease (ACHD) Anatomic Physiologic (AP) classification scheme encompasses both anatomy and physiology to guide care management. To utilize the ACHD AP classification system in population-based research, an International Classification of Diseases (ICD) code-based classification is needed. Methods: AP classification of 240 cases, 18-65 years, with an encounter between 1/1/2010 - 12/31/2019 identified by at least one of 90 CHD codes (41 ICD-9-CM, 49 ICD-10-CM) in a tertiary adult healthcare system was performed by two methods - medical record review and a novel code-based AP classification. Cases were assigned one of four mutually exclusive AP classification categories based on complex vs. non-complex (simple plus moderate) anatomy and combined AB physiology (no/mild physiologic comorbidities) vs. CD physiology (moderate/severe physiologic comorbidities). A composite outcome of death, emergency department visit and/or hospitalization at 1-year after AP classification was evaluated. Results: Both record review and ICD code-based physiology classification methods demonstrated significant differences in 1-year outcomes between AB and CD physiology regardless of anatomic classification (Table 1), with CD physiology experiencing more adverse outcomes. Performance of AP classification by record review [PPV: 85.1% (97/114)] and ICD code-based classification [PPV: 80.7% (92/114)] (p=0.38) was similar. No differences were revealed by comparing outcome prediction within physiologic group by method, (AB by record review vs. AB by ICD codes: p=0.98; CD record review vs. CD by ICD codes: p=0.16). Conclusion: An ICD code-based classification of the ACHD AP guidelines is feasible, predictive of future adverse outcomes, and a reliable tool to use in administrative data. ICD code-based AB and CD physiology classifications are a good differentiator of outcomes for both complex and non-complex anatomic groups.

ABSTRACTBackgroundAdministrative data permits analysis of large cohorts but relies on International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification (ICD) codes that may not reflect true congenital heart defects (CHD).Methods1497 cases with at least one encounter between 1/1/2010 – 12/31/2019 in two healthcare systems (one adult, one pediatric) identified by at least one of 87 ICD CHD codes were validated through chart review for the presence of CHD and CHD anatomic group.ResultsInter- and intra-observer reliability averaged > 95%. Positive predictive value (PPV) of ICD codes for CHD was 68.1% (1020/1497) overall, 94.6% (123/130) for cases identified in both healthcare systems, 95.8% (249/260) for severe codes, 52.6% (370/703) for shunt codes, 75.9% (243/320) for valve codes, 73.5% (119/162) for shunt and valve codes, and 75.0% (39/52) for “Other CHD” (7 ICD codes). PPV for cases with >1 unique CHD code was 85.4% (503/589) vs. 56.3% (498/884) for one CHD code. Of cases with secundum atrial septal defect ICD codes 745.5/Q21.1 in isolation, 30.9% (123/398) had a confirmed CHD. Patent foramen ovale was present in 66.2% (316/477) of false positives (FP). The median number of unique CHD-coded encounters was higher for true positives (TP) than FP (2.0; interquartile range [IQR]: 1.0-3.0 vs 1.0; IQR:1.0-1.0, respectively, p<0.0001). TP had younger mean age at first encounter with a CHD code than FP (22.4 years vs 26.3 years, p=0.0017).ConclusionPPV of CHD ICD codes varies by characteristics for detection of CHD by ICD code and anatomic grouping. While an ICD code for severe CHD and/or the presence of a case in more than one data source, regardless of anatomic group, is associated with higher PPV for CHD, most TP cases did not have these characteristics. The development of algorithms to improve accuracy may improve administrative data for CHD surveillance.

The optimal pain management strategy after lung transplantation is unknown. This study compared analgesic outcomes of intercostal nerve blockade by cryoanalgesia (Cryo) versus thoracic epidural analgesia (TEA). Seventy-two patients who underwent bilateral lung transplantation via clamshell incision at our center from 2016 to 2018 were managed with TEA (N = 43) or Cryo (N = 29). We evaluated analgesic-specific complications, opioid use in oral morphine equivalents (OME), and pain scores (0–10) through postoperative day 7. Adjusted linear regression was used to assess for non-inferiority of Cryo to TEA. The overall mean pain scores (Cryo 3.2 vs TEA 3.8, P = 0.21), maximum mean pain scores (Cryo 4.7 vs TEA 5.5, P = 0.16), and the total opioid use (Cryo 484 vs TEA 705 OME, P = 0.12) were similar in both groups, while the utilization of postoperative opioid-sparing analgesia, measured as use of lidocaine patches, was lower in the Cryo group (Cryo 21

Based on a novel dataset of venture capital (VC) funds and startups in China, we study the role of government-funded VCs (GVCs) in supporting entrepreneurship during the U.S.-China trade war. Employing a difference-in-differences strategy, While the trade war resulted in a substantial reduction in the likelihood of independent venture capital (IVC) funds investing in industries with higher trade war exposure, it had little impact on GVCs. Further analysis suggests that GVCs' investment behavior is likely driven by policy initiatives rather than differences in investment expertise or investment and exit opportunities, as technology-intensive companies with heightened trade war exposure were more likely to receive follow-on financing from GVCs. Companies located in prefectures with a higher density of GVC activities filed more patents in response to the trade war shocks, suggesting that a more active presence of GVCs in the local economy results in a "compete-for-financing" effect that mitigates the problem of underinvestment in innovation during economic downturns. Meanwhile, we find limited evidence of misallocations in GVC investments or adverse selection of startups seeking GVC financing in the short-term.

Based on a nationally representative survey on SMEs in China, we study the impact of government policy interventions on SMEs during the COVID-19 pandemic. Our findings are three-fold. First, relief policies in the form of payment deferrals and exemptions significantly improve SMEs' cash flows and further stimulate their operational recovery. This effect is more pronounced for firms with larger shares of high-skilled employees. Second, financial support policies do not appear to be effective in alleviating SMEs' cash constraints or encouraging the reopening of small businesses, potentially due to difficulties in accessing policy-oriented loans and misallocation of credit. Last, regional and local lock-down policies decrease SMEs' incidence of reopening and delay their expected reopening in the near future, likely by reducing consumer demand. Our findings shed new light on the policy debates on supporting SMEs during the COVID-19 pandemic.

Airway infections are difficult to distinguish from acute rejection in lung transplant recipients. Traditional culture techniques take time that may delay treatment. We hypothesized that a rapid multiplex molecular assay could improve time to diagnosis and appropriate clinical decision making. In a prospective observational study of recipients undergoing bronchoscopy, we assessed the BioFire ® FilmArray ® Pneumonia Panel (BFPP) in parallel to standard of care (SOC) diagnostics. Research clinicians performed shadow (research only) clinical decision making in real time. Time to report and interpretation were reported as median and interquartile ranges and compared by Wilcoxon signed-ranked test. Agreement was defined based on detection of any species targeted in the molecular assay. For the 150 enrolled subjects, BFPP results were available 3.8 hours (IQR 2.8–5.1) following bronchoscopy, compared to 13 hours for viral SOC (IQR 10–34, P  < .001) results and 48 hours for bacterial SOC (IQR 46–70, P  < .001) results. Positive BFPP results were interpreted in 9 hours (IQR 5–20) following bronchoscopy, compared to 74 hours for SOC (IQR 37–110, P  < .001). Assays agreed for 138 (92%) of the 150 subjects. Of 22 BFPP diagnoses, five (23%) resulted in a shadow antibiotic recommendation. Notable BFPP deficiencies included fungal species and H parainfluenzae , accounting for 15 (27%) and 13 (23%) of the 56 actionable SOC results, respectively. This molecular diagnostic including bacterial targets has the potential to shorten time to diagnosis and augment current clinical decision making but cannot replace SOC culture methods.

The use of donor lungs from victims of drowning remains a rare occurrence, given concerns over lung parenchymal injury and microbial contamination secondary to aspiration. Given this infrequency, there is a relative paucity of literature surrounding the use of organs from drowned donors, with the few that exist on this subject focusing primarily on cases of drowning in naturally occurring bodies of water (i.e., drowning at sea). Little is known regarding the outcomes of utilizing donor lungs from victims of drowning in artificial bodies of water (i.e., swimming pools). Here, we describe three cases of bilateral lung transplantation from donors who drowned in swimming pools, with good short- and long-term outcomes. These cases lend further evidence to the feasibility of using such organs that have traditionally been viewed with much trepidation. With continually growing demand for donor organs, the use of drowned donor lungs may serve as a means to expand the donor pool and lessen the burden of waitlist mortality.

PURPOSE OF REVIEW:Despite an increase in lung transplantation globally, the waitlist mortality persists due to organ shortage. In order to keep up with the demand, the marginal lung donor criteria need to be revisited. The goal of this review is to redefine the lung donor criteria based on the most recent data.RECENT FINDINGS:Recent evidence indicates that lungs from donor with traditional extended criteria such as, age more than 55, PaO2/FiO2 threshold of less than 300, ischemia time more than 6 h, positive sputum microbiology, abnormal radiography no longer represent contraindications to lung transplantation by themselves. In addition, the introduction of new antiviral agents, organs from Hepatitis C positive donors, though not extended in the traditional sense, have shown positive outcomes.SUMMARY:The decision to use such organs, including those with smoking history, should be taken in totality weighing both donor and recipient characteristics. Hence, authors would advocate removing the term 'marginal' or 'extended' from lung donor criteria.