Effectiveness of Colonoscopy in Reducing Incidence of Late-stage Colorectal Cancer Within an Opportunistic Screening Program.

BACKGROUND: The effectiveness of colonoscopy in preventing colorectal cancer (CRC) within opportunistic screening programs has not been clearly established. The aim of this study was to analyze the effectiveness of colonoscopy within an opportunistic screening program using nested case-control study. METHODS: Subjects who received a diagnosis of CRC (CG) between the ages of 50 and 90 years were included and matched by age and gender in a 1:5 ratio with patients without CRC diagnosis (COG) during the period 2015 to 2023. Using conditional regression analyses, we tested the association between screening colonoscopy and CRC. Subgroup analyses were then performed for CRC location, endoscopist specialty, and colonoscopy quality. RESULTS: Of the 134 patients in CG, 19 (14.18%) had a colonoscopy in the preceding 5 years compared with 258 out of 670 (38.51%) in COG (AOR, 0.24; 95% CI: 0.14-0.41). Any colonoscopy was strongly associated with decreased odds for left-sided CRC (AOR, 0.09; 95% CI: 0.04-0.24) but not for right-sided CRC (AOR, 0.58; 95% CI: 0.29-1.17). Only complete colonoscopy (AOR, 0.41; 95% CI: 0.19-0.89) and colonoscopy with satisfactory bowel preparation (AOR, 0.38; 95% CI: 0.15-0.98) were associated with decreased odds for right-sided CRC. No significant differences in colonoscopy outcomes were found when stratifying by endoscopist specialty. CONCLUSIONS: In the setting of an opportunistic screening program, exposure to any colonoscopy significantly reduced left-sided CRC incidence; however, only high-quality colonoscopy was associated with a lower incidence of right-sided CRC. Therefore, every possible effort should be made to optimize the quality and cost-effectiveness of colonoscopy within an opportunistic screening program.

Experiences of Racism in School and Associations with Mental Health, Suicide Risk, and Substance Use Among High School Students - Youth Risk Behavior Survey, United States, 2023.

Racism is a fundamental determinant of health inequities among racial and ethnic groups and is understudied among adolescents. In 2023, the national Youth Risk Behavior Survey questionnaire included an item assessing experiences of racism in the school setting among students in grades 9-12 in the United States. This report estimates the prevalence of students who reported ever having experienced racism in school and compares prevalence by racial and ethnic groups. For each racial and ethnic group, prevalence differences and prevalence ratios were estimated comparing the prevalence of indicators of poor mental health, suicide risk, and substance use among students who reported that they have ever versus never experienced racism in school. In 2023, approximately one in three high school students (31.5%) said that they had ever experienced racism in school. Reported experiences of racism were most prevalent among Asian (56.9%), multiracial (48.8%), and Black or African American (Black) (45.9%) students and least prevalent among White students (17.3%). Black and Hispanic or Latino (Hispanic) students who reported experiencing racism had a higher prevalence of all health risk behaviors and experiences investigated, including indicators of poor mental health, suicide risk, and substance use compared with students of their racial and ethnic group who reported never experiencing racism. Many of these associations were also found among multiracial and White students. Student reports of racism were associated with indicators of mental health and suicide risk among American Indian or Alaska Native (AI/AN) and Asian students. Among students of color, including AI/AN, Asian, Black, Hispanic, and multiracial students, the prevalence of seriously considering and attempting suicide was more than two times higher among students who ever compared with never experienced racism. These findings demonstrate that racism in the school setting is experienced by high school students attending public and private schools and continues to disproportionately affect students of color. Students who reported experiencing racism had a higher prevalence of indicators of poor mental health, suicide risk, and substance use. Schools can incorporate policies and practices to prevent unfair treatment on the basis of race and ethnicity and offer resources to help students cope with these experiences.

Disparities in School Connectedness, Unstable Housing, Experiences of Violence, Mental Health, and Suicidal Thoughts and Behaviors Among Transgender and Cisgender High School Students - Youth Risk Behavior Survey, United States, 2023.

Transgender high school students (those whose gender identity differs from their sex assigned at birth) experience disparate health outcomes and challenges in school, including violence and discrimination, compared with cisgender students (those whose gender identity aligns with their sex assigned at birth). Until recently, population-based data describing the experiences of transgender students and students questioning whether they are transgender (questioning) have been limited. In 2023, the national Youth Risk Behavior Survey assessed transgender identity, providing the first nationally representative data about transgender students. This report describes the demographic characteristics of transgender and questioning high school students and examines differences in the prevalence of experiences of violence, poor mental health, suicidal thoughts and behaviors, school connectedness, and unstable housing among transgender, questioning, and cisgender high school students nationwide. In 2023, 3.3% of U.S. high school students identified as transgender, and 2.2% identified as questioning. Transgender and questioning students experienced a higher prevalence of violence, poor mental health, suicidal thoughts and behaviors, and unstable housing, and a lower prevalence of school connectedness than their cisgender peers. Compared with 8.5% of cisgender male students, 25.3% of transgender students and 26.4% of questioning students skipped school because they felt unsafe. An estimated 40% of transgender and questioning students were bullied at school, and 69% of questioning students and 72% of transgender students experienced persistent feelings of sadness or hopelessness, a marker for experiencing depressive symptoms. Approximately 26% of transgender and questioning students attempted suicide in the past year compared with 5% of cisgender male and 11% of cisgender female students. Intervention opportunities for schools to create safer and more supportive environments for transgender and questioning students can help address these disparities. The findings of this report suggest that more effort is necessary to ensure that the health and well-being of youths who are socially marginalized is prioritized.

The impact of single-port robotic surgery: a survey among urology residents and fellows in the United States.

Our aim was to investigate the perception and future expectations of Single-Port (SP) surgery among urology trainees in the United States. A 34-item online survey was distributed to urological residency and fellowship programs across the US, covering demographic profiles, SP training opportunities, perceived educational impact, and future perspectives. Descriptive analysis and multivariable linear regression were used to assess predictors of SP adoption. 201 surveys were completed (28.6% completion rate). Among institutions with an SP platform, about 50% have used it regularly for over 2 years, though often in less than 50% of procedures. While robotic simulators are commonly available, only 17% offer both multi-port and SP simulators, and structured pre-clinical SP training is limited. Approximately 30% of respondents expressed concerns over limited hands-on experience and a steeper learning curve with SP. Around 40% felt that their robotic surgery exposure was negatively impacted by SP's introduction. SP surgery's benefits are seen mostly in the immediate post-operative period and a significant number of respondents foresee a major role for SP in urology. However, proficiency in SP surgery is not seen as crucial for career advancement or job opportunities. Academic job aspirations, SP platform availability, and SP surgery workload are predictors of future SP implementation. Trainees increasingly recognize the clinical benefits of SP procedures but express concerns about the potential negative impact on hands-on experience. Training programs should more systematically integrate SP technology into curricula. There is a correlation between training in high-volume SP centers and future SP adoption.

Return to Intended Oncological Therapy: State of the Art and Perspectives.

PURPOSE OF THE REVIEW: Despite advances in surgical procedures, cancer recurrence still affects a substantial proportion of patients for whom surgery is considered a curative therapy. This review aims to provide a comprehensive overview of RIOT, addressing its definition, influencing factors, and clinical implications. FINDINGS: RIOT can be defined as a continuous variable as the time from surgery to initiation of adjuvant therapies or categorically as whether patients can successfully receive adjuvant therapies or not. Factors influencing RIOT are age, sex, socioeconomic status, access to healthcare, physical performance and comorbidities, and quality of anesthesia and surgical care. Adjuvant therapies such as chemotherapy, radiotherapy, and immunotherapy are often administered to reduce the risk of recurrence after surgery and improve survival. Return to intended oncologic therapy (RIOT) has emerged as a promising outcome metric reflecting patients' functional recovery after surgery and their ability to receive adjuvant therapies.

Clinical associations with treatment resistance in depression: An electronic health record study.

Treatment resistance is common in major depressive disorder (MDD), yet clinical risk factors are not well understood. Using a discovery-replication design, we conducted phenome-wide association studies (PheWASs) of MDD treatment resistance in two electronic health record (EHR)-linked biobanks. The PheWAS included participants with an MDD diagnosis in the EHR and at least one antidepressant (AD) prescription. Participant lifetime diagnoses were mapped to phecodes. PheWASs were conducted for three treatment resistance outcomes based on AD prescription data: number of unique ADs prescribed, ≥1 and ≥2 CE switches. Of the 180 phecodes significantly associated with these outcomes in the discovery cohort (n = 12,558), 71 replicated (n = 8,206). In addition to identifying known clinical factors for treatment resistance in MDD, the total unique AD prescriptions was associated with additional clinical variables including irritable bowel syndrome, gastroesophageal reflux disease, symptomatic menopause, and spondylosis. We calculated polygenic risk of specific-associated conditions and tested their association with AD outcomes revealing that genetic risk for many of these conditions is also associated with the total unique AD prescriptions. The number of unique ADs prescribed, which is easily assessed in EHRs, provides a more nuanced measure of treatment resistance, and may facilitate future research and clinical application in this area.

Adults born preterm have lower peripheral skeletal muscle area and strength.

Prematurity is associated with lower exercise capacity, which relies on the integrity of the cardiovascular, pulmonary, and skeletal muscle systems. Our animal model mimicking prematurity-associated conditions showed altered muscle composition and atrophy in adulthood. This study aimed to compare muscle composition and strength in adults born preterm versus full-term controls. This observational cohort study recruited 55 adults born preterm, ≤ 29 weeks' of gestation and 53 full-term controls who underwent musculoskeletal ultrasound imaging to assess morphology of the rectus femoris at rest and during a maximal voluntary contraction. Maximal voluntary contraction of the hands and legs were measured by manual dynamometry. In adults born preterm, there was lower muscle strength (handgrip: - 4.8 kg, 95% CI - 9.1, - 0.6; knee extensor: - 44.6 N/m, 95% CI - 63.4, - 25.8) and smaller muscle area (- 130 mm2, 95% CI - 207, - 53), which was more pronounced with a history of bronchopulmonary dysplasia. Muscle stiffness was increased in the preterm versus term group (0.4 m/s, 95% CI 0.04, 0.7). Prematurity is associated with alterations in skeletal muscle composition, area, and function in adulthood. These findings highlight the necessity to implement preventive and/or curative approaches to improve muscle development and function following preterm birth to enhance overall health in this population.

A structural determinant of the behavior of water at hydration and nanoconfinement conditions.

The molecular nature of the phases that conform the two-liquid scenario is elucidated in this work in the light of a molecular principle governing water structuring, which unveils the relevance of the contraction and reorientation of the second molecular shell to allow for the existence of coordination defects in water's hydrogen bond network. In turn, such principle is shown to also determine the behavior of hydration and nanoconfined water while enabling to define conditions for wettability (quantifying hydrophobicity and predicting drying transitions), thus opening the possibility to unravel the active role of water in central fields of research.

Preclinical Evaluation of AZD6422, an Armored Chimeric Antigen Receptor T Cell Targeting CLDN18.2 in Gastric, Pancreatic, and Esophageal Cancer.

PURPOSE: CLDN18.2 is a surface membrane protein crucial for maintaining tight junctions in gastric mucosal cells and is highly expressed in gastric, esophageal, and pancreatic cancers. Thus, CLDN18.2 is suited for exploration as a clinical target for chimeric antigen receptor T-cell (CAR-T) therapy in these indications. Although CAR-T therapies show promise, a challenge faced in their development for solid tumors is the immunosuppressive tumor microenvironment, often characterized by the presence of immune and stromal cells secreting high levels of transforming growth factor beta (TGF-ß). Addition of TGF-ß armoring can potentially expand CAR-T activity in solid tumors. We report on the preclinical development of a CLDN18.2-targeting CAR-T showing effectiveness in CLDN18.2-positive gastric, esophageal, and pancreatic tumor models. EXPERIMENTAL DESIGN: The lead lentivirus product contains a unique single-chain variable fragment, CD28 and CD3z costimulatory and signaling domains, and dominant negative TGF-ß receptor armoring, enhancing targeting and safety and counteracting suppression. We developed a shortened cell manufacturing process to enhance the potency of the final product, AZD6422. RESULTS: AZD6422 exhibited significant antitumor activity and tolerability in multiple patient-derived tumor xenograft models with various CLDN18.2 and TGF-ß levels, as determined by immunohistochemistry. Efficacy of armored CAR-Ts in tumor models with elevated TGF-ß was increased in vitro and in vivo. In vitro restimulation assays established greater persistence and cytolytic function of AZD6422 compared with a traditionally manufactured CAR-T. CONCLUSIONS: AZD6422 was safe and efficacious in patient-derived, CLDN18.2-positive murine models of gastrointestinal cancers. Our data support further clinical development of AZD6422 for patients with these cancers.

APPLICATIONS OF MULTIMODAL GENERATIVE ARTIFICIAL INTELLIGENCE IN A REAL-WORLD RETINA CLINIC SETTING.

PURPOSE: This study evaluates a large language model, Generative Pre-trained Transformer 4 with vision, for diagnosing vitreoretinal diseases in real-world ophthalmology settings. METHODS: A retrospective cross-sectional study at Bascom Palmer Eye Clinic, analyzing patient data from January 2010 to March 2023, assesses Generative Pre-trained Transformer 4 with vision's performance on retinal image analysis and International Classification of Diseases 10th revision coding across 2 patient groups: simpler cases (Group A) and complex cases (Group B) requiring more in-depth analysis. Diagnostic accuracy was assessed through open-ended questions and multiple-choice questions independently verified by three retina specialists. RESULTS: In 256 eyes from 143 patients, Generative Pre-trained Transformer 4-V demonstrated a 13.7% accuracy for open-ended questions and 31.3% for multiple-choice questions, with International Classification of Diseases 10th revision code accuracies at 5.5% and 31.3%, respectively. Accurately diagnosed posterior vitreous detachment, nonexudative age-related macular degeneration, and retinal detachment. International Classification of Diseases 10th revision coding was most accurate for nonexudative age-related macular degeneration, central retinal vein occlusion, and macular hole in OEQs, and for posterior vitreous detachment, nonexudative age-related macular degeneration, and retinal detachment in multiple-choice questions. No significant difference in diagnostic or coding accuracy was found in Groups A and B. CONCLUSION: Generative Pre-trained Transformer 4 with vision has potential in clinical care and record keeping, particularly with standardized questions. Its effectiveness in open-ended scenarios is limited, indicating a significant limitation in providing complex medical advice.

Introducing a New Severity Specifier for Schizophrenia: Conceptual Framework and Clinical Implications.

Schizophrenia patients represent a heterogeneous group in clinical presentation and severity. Although severity has been operationalized in different ways, mostly on a gradient between symptom severity and functional impairment, such approaches are limited in capturing real-world functioning. We suggest adopting the severity model proposed by DSM-5 for autism spectrum disorders. The model defines three levels of severity, based on the support required, directly addressing two barriers from previous models: real-world functioning and ease of implementation. Our adapted model includes three new features: First, this severity specifier is global, rather than for each symptom domain. Second, the centrality of occupational functioning is emphasized to define the level of support. Third, we propose a one-month timeframe for severity appraisal, standardizing the assessment process. Considering practical utility, we indicate how severity assessment can guide clinical practice towards rehabilitation. Additionally, we outlined operational definitions for severity and functioning in schizophrenia, aligned with the premises of our model. Finally, we acknowledge potential limitations, the most relevant being the need for empirical validation. The model is presented to foster discussion. Additional studies will follow to investigate inter-rater reliability and convergent validation with standard measures of symptom and functioning severity.

Cross-Sectional Survey of Vitreoretinal Surgery Fellowship Training in Secondary Intraocular Lens Placement.

Purpose: To assess current trends in vitreoretinal surgical fellowship training for placement of secondary intraocular lenses (IOLs). Methods: A cross-sectional survey was administered to vitreoretinal surgical fellowship graduates who completed their program between 2019 and 2023. Results: Completed responses were obtained from 70 (22.5%) of 311 eligible recipients. Training settings included academic (80%), hybrid academic/private practice (15%), and private practice (5%). During their fellowship, the majority of respondents reported 10 or fewer cases using anterior chamber (AC) IOLs (69%), 5 to 50 cases using scleral-sutured IOLs (64%), and 5 to 25 cases using sutureless scleral-fixated IOLs (52%). Most fellows (79%) did not have exposure to iris-fixated IOL placement during fellowship training. The Akreos AO60 (78%) and Envista MX60 (10%) IOLs were the most common choice for scleral-sutured placement. Most fellows (67%) placed fewer than 10 secondary IOLs through scleral tunnels. Overall, scleral-sutured IOL placement (Akreos Gore-Tex [polytetrafluoroethylene] sutured, 49%) and scleral-fixated IOLs (modified Yamane, 45%) were the preferred and most comfortable surgical techniques for recent graduates after completing training. There was a significant association between surgical case volume during fellowship training and self-reported competency for each type of secondary IOL (P ≤ .005). Conclusions: The majority of vitreoretinal surgical fellows receive limited training in the placement of AC IOLs or construction of scleral tunnels during their fellowship. Aligned with their experience during fellowship, recent graduates generally prefer implanting scleral-fixated or scleral-sutured IOLs. Analysis of trainees' exposure to various techniques and postgraduate surgical preferences may identify areas for improvement in surgical education.

Assessment of dual time point protocols to produce parametric Ki images in FDG PET/CT: A virtual clinical study.

PURPOSE: This simulation study investigated the feasibility of generating Patlak Ki images using a dual time point (DTP-Ki) scan protocol involving two 3-min/bed routine static PET scans and, subsequently, assessed DTP-Ki performance for an optimal DTP scan time frame combination, against conventional Patlak Ki estimated from complete 0-93 min dynamic PET data. METHODS: Six realistic heterogeneous tumors of different characteristic spatiotemporal [18F]FDG uptake distributions for three noise levels commonly found in clinical studies and 20 noise realizations (N = 360 samples) were produced by analytic simulations of the XCAT phantom. Subsequently, DTP-Ki images were generated by performing standard linear indirect Patlak analysis with t* ≥ 12 $ \ge 12$ -min (Patlakt* = 12) using a scaled population-based input function (sPBIF) model on 66 combinations of early and late 3-min/bed static whole-body PET reconstructed images. All DTP-Ki images were evaluated against respective DTP-Ki images estimated with Patlakt* = 12 and 0-93 min individual input functions (iIFs) and against gold standard Ki images estimated with Patlakt* = 12, 0-93 min iIFs and tissue time activity curves from all reconstructed WB passes 12-93 min post injection. The optimal combination of early and late frames, in terms of attaining the highest correlation between DTP-Ki with sPBIF and gold standard Ki was also determined from a set of 66 different combinations of 2-min early and late frames. Moreover, the performance of DTP-Ki with sPBIF was compared against that of the retention index (RI) in terms of their correlation to the gold standard Ki. Finally, the feasibility and practicality of DTP protocol in the clinic were assessed through the analysis of nine patients. RESULTS: High correlations (>0.9) were observed between DTP-Ki values from sPBIF and those from iIFs for all evaluated DTP protocols while the mean AUC difference between sPBIF and iIFs was less than 10%. The percentage difference of mean values between DTP-Ki from sPBIF and from iIFs was less than 1%. DTP Ki from sPBIF exhibited significantly higher correlation with gold standard Ki, in contrast to RI, across all 66 DTP protocols (p < 0.05 using the two-tailed t-test by Williams) with the highest correlation attained for the 50-53-min early + 90-93-min late scan time frames (optimal DTP protocol). CONCLUSION: Feasibility of generating Patlak Ki [18F] FDG images from an early and a late post injection 3-min/bed routine static scan using a population-based input function model was demonstrated and an optimal DTP scan protocol was determined. The results indicated high correlations between DTP-Ki and gold-standard Ki images that are significantly larger than those between RI and gold-standard Ki.

Electrical Stimulation Prevents Muscular Atrophy and the Decrease of Interleukin-6 in Paralyzed Muscles after Spinal Cord Injury in Rats.

Objective To analyze the muscle trophism and expression of interleukin-6 in the biceps brachii muscle of rats with incomplete cervical spinal cord injury treated with neuromuscular electrical stimulation (NMES). Methods Adult rats underwent C5-C7 spinal cord hemisection and a 5-week NMES protocol. Trophism of the biceps brachii was assessed using muscle weight/body weight ratio and histological analysis. Interleukin-6 expression from biceps brachii was measured using the enzyme-linked immunosorbent assay technique. Results Preservation of the biceps brachii muscle trophism was found in the NMES treated group, along with prevention of the reduction of interleukin-6 levels. Conclusion Spinal cord injury causes muscle atrophy and decreases interleukin-6 levels. These alterations are partially prevented by NMES. The results suggest a possible NMES action mechanism and underscore the clinical use of this therapeutic tool.

Plasma Adsorption with the MTx.100 Column in Critically Ill COVID-19 Patients: A Prospective Study and Propensity Score Analysis.

BACKGROUND: Early in the COVID-19 pandemic, patients with severe disease admitted to the intensive care unit (ICU) had a high incidence of mortality. We aimed to investigate whether plasma adsorption with the MTx.100 Column could improve survival. METHODS: We performed a prospective, single-arm, multicenter, Emergency Use Authorization (EUA) trial in patients admitted to the ICU with severe COVID-19 who were worsening despite standard therapy. The primary outcome was all-cause mortality on day 28. Outcomes were analyzed using both a pre-specified performance goal (PG), and a propensity score-matched (PSM) analysis from the highest enrolling center, in which patients treated with the standard of care (SOC) plus the MTx.100 Column (n = 70) were compared to a contemporaneous cohort treated at the same center with SOC only (n = 244). FINDINGS: Between May 21, 2020, and November 2, 2021, 107 patients with severe COVID-19 (mean age 58.1) at 7 US centers were enrolled and had at least one plasma adsorption treatment initiated. All-cause mortality on day 28 was 37.4% (40/107), an improvement over the prespecified PG (88.1%, p < 0.0001). There were no serious adverse events attributable to the MTx.100 Column or plasmapheresis. Improvements in most metabolic and inflammatory markers were also noted. The PSM analysis showed that survival odds were three times higher for MTx.100 Column-treated patients (95% CI: 1.56-5.88) than for those treated with SOC only. INTERPRETATION: The MTx.100 Column treatment in severe COVID-19 resulted in a lower mortality than SOC by both pre-specified PG and PSM analysis. TRIAL REGISTRATION: clinicaltrials.gov (NCT04358003).

Single-Port Extraperitoneal vs. Multiport Transperitoneal Robot-Assisted Radical Prostatectomy: A Propensity Score-Matched Analysis.

(1) Background: Since the introduction of the purpose-built Single Port (SP) robotic platform, there has been an ongoing debate regarding its advantages compared to the established multi-port (MP) system. The goal of this present study is to compare the perioperative, oncological, and functional outcomes of SP Extraperitoneal robotic radical prostatectomy (RARP) versus that of MP Transperitoneal RARP approach at a high-volume tertiary center. (2) Methods: Based on a retrospective review of the prospectively maintained IRB-approved database, 925 patients successfully underwent RARP by a single experienced robotic surgeon. A 4:1 propensity-matched analysis based on the baseline prostate cancer International Society of Urological Pathology (ISUP) Grade Group, clinical stage, and preoperative Prostate Specific Antigen (PSA) was performed, which yielded a cohort of 606 patients-485 in the SP EP and 121 in the MP TP approaches. Of note, the SP EP approach also included the traditional Extraperitoneal (n = 259, 53.4%) and the novel Transvesical (TV) approaches (n = 226, 46.6%). (3) Results: The overall operative time was slightly longer in the SP cohort, with a mean of 198.9 min compared to 181.5 min for the MP group (p < 0.001). There were no intraoperative complications with the MP approach and only one during the SP approach. The SP EP technique demonstrated significant benefits, encompassing reduced intraoperative blood loss (SP 125.1 vs. MP 215.9 mL), shorter length of hospital stay (SP 12.6 vs. MP 31.9 h), reduced opioid use at the time of discharge (SP 14.4% vs. MP 85.1%), and an earlier Foley catheter removal (SP 6 vs. MP 8 days). From an oncological perspective, the rate of positive surgical margins remained comparable across both groups (p = 0.84). Regarding functional outcomes, the mean continence rates and Sexual Health Inventory for Men (SHIM) scores were identical between the two groups at 6 weeks, 3 months, and 6 months respectively. (4) Conclusion: SP EP RARP demonstrates similar performance to MP TP RARP in terms of oncologic and functional outcomes. However, SP EP RARP offers several advantages in reducing the overall hospital stay, decreasing postoperative pain and hence the overall opioid use, as well as shortening the time to catheter removal, all of which translates to reduced morbidity and facilitates the transition to outpatient surgery.

Prediction of medical admissions after psychiatric inpatient hospitalization in bipolar disorder: a retrospective cohort study.

Objective: Bipolar Disorder (BD) is a severe mental illness associated with high rates of general medical comorbidity, reduced life expectancy, and premature mortality. Although BD has been associated with high medical hospitalization, the factors that contribute to this risk remain largely unexplored. We used baseline medical and psychiatric records to develop a supervised machine learning model to predict general medical admissions after discharge from psychiatric hospitalization. Methods: In this retrospective three-year cohort study of 71 patients diagnosed with BD (mean age=52.19 years, females=56.33%), lasso regression models combining medical and psychiatric records, as well as those using them separately, were fitted and their predictive power was estimated using a leave-one-out cross-validation procedure. Results: The proportion of medical admissions in patients with BD was higher compared with age- and sex-matched hospitalizations in the same region (25.4% vs. 8.48%). The lasso model fairly accurately predicted the outcome (area under the curve [AUC]=69.5%, 95%C.I.=55-84.1; sensitivity=61.1%, specificity=75.5%, balanced accuracy=68.3%). Notably, pre-existing cardiovascular, neurological, or osteomuscular diseases collectively accounted for more than 90% of the influence on the model. The accuracy of the model based on medical records was slightly inferior (AUC=68.7%, 95%C.I. = 54.6-82.9), while that of the model based on psychiatric records only was below chance (AUC=61.8%, 95%C.I.=46.2-77.4). Conclusion: Our findings support the need to monitor medical comorbidities during clinical decision-making to tailor and implement effective preventive measures in people with BD. Further research with larger sample sizes and prospective cohorts is warranted to replicate these findings and validate the predictive model.

Estimated Health and Economic Outcomes of Racial and Ethnic Tuberculosis Disparities in US-Born Persons.

Importance: Despite significant progress made toward tuberculosis (TB) elimination, racial and ethnic disparities persist in TB incidence and case-fatality rates in the US. Objective: To estimate the health outcomes and economic cost of TB disparities among US-born persons from 2023 to 2035. Design, Setting, and Participants: Generalized additive regression models projecting trends in TB incidence and case-fatality rates from 2023 to 2035 were fit based on national TB surveillance data for 2010 to 2019 in the 50 US states and the District of Columbia among US-born persons. This baseline scenario was compared with alternative scenarios in which racial and ethnic disparities in age- and sex-adjusted incidence and case-fatality rates were eliminated by setting rates for each race and ethnicity to goal values. Additional scenarios were created examining the potential outcomes of delayed reduction of racial and ethnic disparities. The potential benefits of eliminating disparities from differences between baseline and alternative scenario outcomes were quantified. Data were analyzed from January 2010 to December 2019. Exposures: Non-Hispanic American Indian or Alaska Native, non-Hispanic Asian, non-Hispanic Black, Hispanic, non-Hispanic Native Hawaiian or Other Pacific Islander, or non-Hispanic White race and ethnicity. Main outcomes and measures: TB cases and deaths averted, quality-adjusted life years gained, and associated costs from a societal perspective. Results: The study included 31 811 persons with reported TB from 2010 to 2019 (mean [SD] age, 47 [24] years; 20 504 [64%] male; 1179 [4%] American Indian or Alaska Native persons; 1332 [4%] Asian persons; 12 152 [38%] Black persons; 6595 [21%] Hispanic persons; 299 [1%] Native Hawaiian or Other Pacific Islander persons; and 10 254 [32%] White persons). There were 3722 persons with a reported TB death. Persistent racial and ethnic disparities were associated with an estimated 11 901 of 26 203 TB cases among US-born persons (45%; 95% uncertainty interval [UI], 44%-47%), 1421 of 3264 TB deaths among US-born persons (44%; 95% UI, 39%-48%), and an economic cost of $914 (95% UI, $675-$1147) million from 2023 to 2035. Delayed goal attainment reduced the estimated avertable TB outcomes by 505 (95% UI, 495-518) TB cases, 55 (95% UI, 51-59) TB deaths, and $32 (95% UI, $24-$40) million in societal costs annually. Conclusions and relevance: In this modeling study of racial and ethnic disparities of TB, these disparities were associated with substantial future health and economic outcomes of TB among US-born persons without interventions beyond current efforts. Actions to eliminate disparities may reduce the excess TB burden among these persons and may contribute to accelerating TB elimination within the US.

Improving the contribution of mathematical modelling evidence to guidelines and policy: Experiences from tuberculosis.

We read with great interest the recent paper by Lo et al., who argue that there is an urgent need to ensure the quality of modelling evidence used to support international and national guideline development. Here we outline efforts by the Tuberculosis Modelling and Analysis Consortium, together with the World Health Organization Global Task Force on Tuberculosis Impact Measurement, to develop material to improve the quality and transparency of country-level tuberculosis modelling to inform decision-making.

Projected health and economic effects of a pan-tuberculosis treatment regimen: a modelling study.

BACKGROUND: A pan-tuberculosis regimen that could be initiated without knowledge of drug susceptibility has been proposed as an objective of tuberculosis regimen development. We modelled the health and economic benefits of such a regimen and analysed which of its features contribute most to impact and savings. METHODS: We constructed a mathematical model of tuberculosis treatment parameterised with data from the published literature specific to three countries with a high tuberculosis burden (India, the Philippines, and South Africa). Our model simulated cohorts of newly diagnosed tuberculosis patients, including drug susceptibility testing if performed, regimen assignment, discontinuation, adherence, costs, and resulting outcomes of durable cure (microbiological cure without relapse), need for retreatment, or death. We compared a pan-tuberculosis regimen meeting the WHO 2023 target regimen profile against the standard of care of separate rifampicin-susceptible and rifampicin-resistant regimens. We estimated incremental cures; averted deaths, secondary cases, and costs; and prices below which a pan-tuberculosis regimen would be cost saving. We also assessed scenarios intended to describe which mechanisms of benefit from a pan-tuberculosis regimen (including improved characteristics compared with the current rifampicin-susceptible and rifampicin-resistant regimens and improved regimen assignment and retention in care for patients with rifampicin-resistant tuberculosis) would be most impactful. Results are presented as a range of means across countries with the most extreme 95% uncertainty intervals (UIs) from the three UI ranges. FINDINGS: Compared with the standard of care, a pan-tuberculosis regimen could increase the proportion of patients durably cured after an initial treatment attempt from 69-71% (95% UI 57-80) to 75-76% (68-83), preventing 30-32% of the deaths (20-43) and 17-20% of the transmission (9-29) that occur after initial tuberculosis diagnosis. Considering savings to the health system and patients during and after the initial treatment attempt, the regimen could reduce non-drug costs by 32-42% (22-49) and would be cost saving at prices below US$170-340 (130-510). A rifamycin-containing regimen that otherwise met pan-tuberculosis targets yielded only slightly less impact, indicating that most of the benefits from a pan-tuberculosis regimen resulted from its improvements upon the rifampicin-susceptible standard of care. Eliminating non-adherence and treatment discontinuation, for example via a long-acting injectable regimen, increased health impact and savings. INTERPRETATION: In countries with a high tuberculosis burden, a shorter, highly efficacious, safe, and tolerable regimen to treat all tuberculosis could yield substantial health improvements and savings. FUNDING: Bill & Melinda Gates Foundation.