Clinical decision support systems in addiction and concurrent disorders: A systematic review and meta-analysis.

INTRODUCTION: This review aims to synthesise the literature on the efficacy, evolution, and challenges of implementing Clincian Decision Support Systems (CDSS) in the realm of mental health, addiction, and concurrent disorders. METHODS: Following PRISMA guidelines, a systematic review and meta-analysis were performed. Searches conducted in databases such as MEDLINE, Embase, CINAHL, PsycINFO, and Web of Science through 25 May 2023, yielded 27,344 records. After necessary exclusions, 69 records were allocated for detailed synthesis. In the examination of patient outcomes with a focus on metrics such as therapeutic efficacy, patient satisfaction, and treatment acceptance, meta-analytic techniques were employed to synthesise data from randomised controlled trials. RESULTS: A total of 69 studies were included, revealing a shift from knowledge-based models pre-2017 to a rise in data-driven models post-2017. The majority of models were found to be in Stage 2 or 4 of maturity. The meta-analysis showed an effect size of -0.11 for addiction-related outcomes and a stronger effect size of -0.50 for patient satisfaction and acceptance of CDSS. DISCUSSION: The results indicate a shift from knowledge-based to data-driven CDSS approaches, aligned with advances in machine learning and big data. Although the immediate impact on addiction outcomes is modest, higher patient satisfaction suggests promise for wider CDSS use. Identified challenges include alert fatigue and opaque AI models. CONCLUSION: CDSS shows promise in mental health and addiction treatment but requires a nuanced approach for effective and ethical implementation. The results emphasise the need for continued research to ensure optimised and equitable use in healthcare settings.

State-level disparities in cervical cancer prevention and impact on outcomes in the U.S.: A modeling study.

Background: Despite the availability of HPV vaccines for over a decade, coverage across the United States (US) is varied. While some states have made concerted efforts to increase HPV vaccination coverage, most model-based analyses have estimated vaccine impact on the US. We estimated the impact of hypothetical changes in HPV vaccination coverage at the state level for three states with varying levels of HPV vaccination coverage and cervical cancer incidence (California, New York, Texas) using a mathematical model. Methods: We developed a new mathematical model of HPV transmission and cervical cancer tailored to state-level cancer incidence and mortality. We quantified the public health impact of increasing HPV vaccination coverage to 80% by 2025 or 2030 and the effect on time to elimination in the three states. Results: Increasing vaccination coverage to 80% in Texas in 10 years could reduce cervical cancer incidence by 50.9% (95%-CrI: 46.6-56.1%) by 2100. In New York and California, achieving the same coverage could reduce incidence by 27.3% (95%-CrI: 23.9-31.5%) and 24.4% (95%-CrI: 20.0-30.0%), respectively. Achieving 80% coverage in 5 years will slightly increase the reduction. If 2019 vaccination coverage continues, cervical cancer elimination would be reached in the US by 2051 (95%-Crl: 2034-2064). However, the timeline by which individual states reach elimination could vary by decades. Conclusion: Achieving an HPV vaccination coverage target of 80% by 2030 will benefit states with low vaccination coverage and high cervical cancer incidence the most. Our results highlight the value of more geographically focused analyses to inform priorities.

Objective sonographic measurements of renal pelvic diameter and renal parenchymal thickness can identify renal hypofunction and poor drainage in patients with antenatally detected unilateral ureteropelvic junction obstruction.

INTRODUCTION: Hydronephrosis grading systems risk stratify patients with potential ureteropelvic junction obstruction, but only some criteria are measured objectively. Most notably, there is no consensus definition of renal parenchymal thinning. OBJECTIVES: The objective of this study was to assess the association between sonographic measures of renal length, renal pelvic diameter, and renal parenchymal thickness and the outcomes of a)renal hypofunction(differential renal function{DRF} <40%) and b)high-risk renal drainage(T1/2 > 40 min). STUDY DESIGN: An institutional database of patients who had diuretic renograms(DR) for unilateral hydronephrosis was reviewed. Only infants with Society for Fetal Urology(SFU) grades 3/4 hydronephrosis without hydroureter on postnatal sonogram and had a DR within 120 days were included. The following measurement variables were analyzed: anterior posterior renal pelvic diameter(APRPD), renal length(RL), renal parenchymal thickness(PT), minimal renal parenchymal thickness(MPT = shortest distance from mid-pole calyx to parenchymal edge), and renal pyramidal thickness(PyrT). RL, PT, MPT, PyrT measurements were expressed as ratios (hydronephrotic kidney/contralateral kidney). Multivariate logistic regression was performed for each outcome by comparing three separate renal measurement models. Model 1: RLR, APRPD, MPTR; Model 2: RLR, APRPD, PTR, Model 3: RLR, APRPD, PyrTR. Individual performance of variables from the best performing model were assessed via ROC curve analysis. RESULTS: 196 patients were included (107 with SFU grade 3, 89 with SFU grade 4) hydronephrosis. Median patient age was 29[IQR 16,47.2] days. 10% had hypofunction, and 20% had T1/2 > 40 min 90% with hypofunction and 87% with high-risk drainage had SFU4 hydronephrosis. Model 1 exhibited the best performance, but on multivariate analysis, only APRPD and MPTR were independently associated with both outcomes. No other measure of parenchymal thickness reached statistical significance. The odds of hypofunction and high-risk drainage increase 10% per 1 mm increase in APRPD(aOR 1.1 [CI 1.03-1.2], p = 0.005; aOR 1.1 [CI 1.03-1.2], p = 0.003). For every 0.1unit increase in MPTR the odds of hypofunction decrease by 40%(aOR 0.6 [CI 0.4-0.9], p = 0.019); and the odds of high-risk drainage decrease by 30%(aOR 0.7 [CI 0.5-0.9], p = 0.011). Optimal statistical cut-points of APRPD >16 mm and/or MPTR <0.36 identified patients at risk for obstructive parameters on DR. DISCUSSION AND CONCLUSION: Of the sonographic hydronephrosis measurement variables analyzed, only APRPD and MPTR were independently associated with objective definitions of obstruction based on renal function and drainage categories. Patients who maintain APRPD <16 mm and/or MPTR >0.36 can potentially be monitored with renal sonograms as there is >90% chance that they will not have DRF<40% or T1/2 > 40 min.

Pseudomonas aeruginosa Activates Quorum Sensing, Antioxidant Enzymes and Type VI Secretion in Response to Oxidative Stress to Initiate Biofilm Formation and Wound Chronicity.

Pseudomonas aeruginosa (PA) is an opportunistic pathogen frequently isolated from cutaneous chronic wounds. How PA, in the presence of oxidative stress (OS), colonizes chronic wounds and forms a biofilm is still unknown. The purpose of this study is to investigate the changes in gene expression seen when PA is challenged with the high levels of OS present in chronic wounds. We used a biofilm-forming PA strain isolated from the chronic wounds of our murine model (RPA) and performed a qPCR to obtain gene expression patterns as RPA developed a biofilm in vitro in the presence of high levels of OS, and then compared the findings in vivo, in our mouse model of chronic wounds. We found that the planktonic bacteria under OS conditions overexpressed quorum sensing genes that are important for the bacteria to communicate with each other, antioxidant stress genes important to reduce OS in the microenvironment for survival, biofilm formation genes and virulence genes. Additionally, we performed RNAseq in vivo and identified the activation of novel genes/pathways of the Type VI Secretion System (T6SS) involved in RPA pathogenicity. In conclusion, RPA appears to survive the high OS microenvironment in chronic wounds and colonizes these wounds by turning on virulence, biofilm-forming and survival genes. These findings reveal pathways that may be promising targets for new therapies aimed at disrupting PA-containing biofilms immediately after debridement to facilitate the treatment of chronic human wounds.

Criteria for the diagnosis of extranodal extension detected on radiological imaging in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.

Extranodal extension of tumour on histopathology is known to be a negative prognostic factor in head and neck cancer. Compelling evidence suggests that extranodal extension detected on radiological imaging is also a negative prognostic factor. Furthermore, if imaging detected extranodal extension could be identified reliably before the start of treatment, it could be used to guide treatment selection, as patients might be better managed with non-surgical approaches to avoid the toxicity and cost of trimodality therapy (surgery, chemotherapy, and radiotherapy together). There are many aspects of imaging detected extranodal extension that remain unresolved or are without consensus, such as the criteria to best diagnose them and the associated terminology. The Head and Neck Cancer International Group conducted a five-round modified Delphi process with a group of 18 international radiology experts, representing 14 national clinical research groups. We generated consensus recommendations on the terminology and diagnostic criteria for imaging detected extranodal extension to harmonise clinical practice and research. These recommendations have been endorsed by 19 national and international organisations, representing 34 countries. We propose a new classification system to aid diagnosis, which was supported by most of the participating experts over existing systems, and which will require validation in the future. Additionally, we have created an online educational resource for grading imaging detected extranodal extensions.

Comparing Peer-Taught Student Tutors to Faculty-Taught Student Tutors in Educating Medical Students on Musculoskeletal Ultrasound.

INTRODUCTION: In recent years, medical education has witnessed a shift in the integration of ultrasound into the preclinical years of medical school. Given the exponential increase in accessibility to ultrasound technology, students now have the opportunity to create peer learning groups in which ultrasound concepts can be taught from peer to peer, empowering students to work together to integrate ultrasound concepts early in their preclinical education. This project investigates the efficacy of peer-taught student tutors (PTSTs) in imparting the fundamentals of basic ultrasound techniques to first-year medical students in the setting of identifying and labeling upper extremity musculoskeletal (MSK) anatomy.  Methods: First-year medical students were instructed to identify volar forearm structures with an ultrasound probe. Students and instructors were given access to an ultrasound probe, ultrasound gel, an iPad, and a standardized patient. Students were taught either by an ultrasound instructor (UI) or PTST. After a hands-on demonstration by a UI or PTST, participating students were told to take screenshots and label their images as accurately as possible, identifying the aforementioned volar structures on a standardized patient without any feedback. The labeled screenshot images of volar structures were graded based on the ability to clearly visualize the intended structures.  Results: The results of this study compare the efficacy of PTSTs as educators of basic sonographic identification techniques with that of UI faculty members. A chi-square analysis was performed between the images obtained by the UI and PTST students, and there was no statistically significant difference in identification accuracy between the groups (p = 0.7538, 0.1977, 0.1812, 0.301). When using the Mann-Whitney U rank test, there remained no statistically significant difference between the accuracy of the students taught by STs compared to students taught by UIs (p = 0.7744, 0.09538, 0.07547, 0.1846). Another finding showed that students belonging to both teaching groups were generally not able to infer the pathology of volar wrist structures when given pathology identification questions regarding upper extremity ultrasound. Using chi-square with Yates correction, there is no sufficient evidence to justify an association between the ability to answer pathology-based ultrasound questions and instructor type (p = p = 0.6299, 0.8725). CONCLUSIONS: This study supports the interpretation that the capability of first-year medical students to learn novice MSK sonographic identification is independent of whether the educator is a PTST or UI. This interpretation reveals a promising avenue toward the integration of the fundamentals of ultrasound identification early in medical education with little to no concern for the exhaustion of institutional resources. Along with the other well-documented benefits of the utilization of STs in medical school, a peer tutoring system centered on ultrasound skills designed in the way this study describes can be an effective, resource-sparing system that enhances medical students' sonographic capabilities early in their preclinical years.

Understanding Physician's Perspectives on AI in Health Care: Protocol for a Sequential Multiple Assignment Randomized Vignette Study.

BACKGROUND: As the availability and performance of artificial intelligence (AI)-based clinical decision support (CDS) systems improve, physicians and other care providers poised to be on the front lines will be increasingly tasked with using these tools in patient care and incorporating their outputs into clinical decision-making processes. Vignette studies provide a means to explore emerging hypotheses regarding how context-specific factors, such as clinical risk, the amount of information provided about the AI, and the AI result, may impact physician acceptance and use of AI-based CDS tools. To best anticipate how such factors influence the decision-making of frontline physicians in clinical scenarios involving AI decision-support tools, hypothesis-driven research is needed that enables scenario testing before the implementation and deployment of these tools. OBJECTIVE: This study's objectives are to (1) design an original, web-based vignette-based survey that features hypothetical scenarios based on emerging or real-world applications of AI-based CDS systems that will vary systematically by features related to clinical risk, the amount of information provided about the AI, and the AI result; and (2) test and determine causal effects of specific factors on the judgments and perceptions salient to physicians' clinical decision-making. METHODS: US-based physicians with specialties in family or internal medicine will be recruited through email and mail (target n=420). Through a web-based survey, participants will be randomized to a 3-part "sequential multiple assignment randomization trial (SMART) vignette" detailing a hypothetical clinical scenario involving an AI decision support tool. The SMART vignette design is similar to the SMART design but adapted to a survey design. Each respondent will be randomly assigned to 1 of the possible vignette variations of the factors we are testing at each stage, which include the level of clinical risk, the amount of information provided about the AI, and the certainty of the AI output. Respondents will be given questions regarding their hypothetical decision-making in response to the hypothetical scenarios. RESULTS: The study is currently in progress and data collection is anticipated to be completed in 2024. CONCLUSIONS: The web-based vignette study will provide information on how contextual factors such as clinical risk, the amount of information provided about an AI tool, and the AI result influence physicians' reactions to hypothetical scenarios that are based on emerging applications of AI in frontline health care settings. Our newly proposed "SMART vignette" design offers several benefits not afforded by the extensively used traditional vignette design, due to the 2 aforementioned features. These advantages are (1) increased validity of analyses targeted at understanding the impact of a factor on the decision outcome, given previous outcomes and other contextual factors; and (2) balanced sample sizes across groups. This study will generate a better understanding of physician decision-making within this context. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54787.

Hydronephrotic lower moiety of duplex systems: Observations using diuresis renography.

PURPOSE: The purpose of this study is to characterize the prevalence and behavior of hydronephrosis of non-refluxing lower moiety of duplex kidneys using MAG-3 diuresis renography. We compare our data to previous case series and ureteropelvic junction obstruction of single systems. MATERIALS AND METHODS: An IRB-approved database of over 5000 diuresis renograms performed in 2025 patients was queried to identify cases of hydronephrosis of lower moiety of duplex kidneys suspicious for ureteropelvic obstruction, excluding those with hydroureter or reflux. Kidney function and post-furosemide drainage parameters on initial and follow-up diuresis renograms were recorded. Medical records and patient outcomes were reviewed. RESULTS: In total, 19 renal units were identified in 18 patients (11 male, 7 female), age range 0.5 months to 17.8 years, including one patient with bilateral lower moiety hydronephrosis. Initial diuresis renograms in 12 asymptomatic patients (13 renal units) with antenatal hydronephrosis demonstrated varying drainage patterns from normal to obstructed. Follow-up studies showed worsening drainage in 3 patients, who all underwent surgery. Drainage improved in 4 patients and remained unchanged in 5 patients (6 renal units). Of the 6 patients presenting with Dietl's crisis, 5 showed obstructive drainage on initial diuresis renogram, 2/5 with decreased function. All 5 obstructed patients underwent surgery. CONCLUSION: Hydronephrosis of the lower moiety of a duplex system is rare and behaves similarly to single systems. The majority are diagnosed antenatally, display a dynamic nature, and may present with acute obstruction. Diuresis renography is a valuable tool in its evaluation and management.

Vaccination and screening strategies to accelerate cervical cancer elimination in Norway: a model-based analysis.

BACKGROUND: Experts have proposed an 'EVEN FASTER' concept targeting age-groups maintaining circulation of human papillomavirus (HPV). We explored effects of the vaccination component of these proposals compared with cervical cancer (CC) screening-based interventions on age-standardized incidence rate (ASR) and CC elimination (<4 cases/100,000) timing in Norway. METHODS: We used a model-based approach to evaluate HPV vaccination and CC screening scenarios compared with a status-quo scenario reflecting previous vaccination and screening. For cohorts ages 25-30 years, we examined 6 vaccination scenarios that incrementally increased vaccination coverage from current cohort-specific rates. Each vaccination scenario was coupled with three screening strategies that varied screening frequency. Additionally, we included 4 scenarios that alternatively increased screening adherence. Population- and cohort-level outcomes included ASR, lifetime risk of CC, and colposcopy referrals. RESULTS: Several vaccination strategies coupled with de-intensified screening frequencies lowered ASR, but did not accelerate CC elimination. Alternative strategies that increased screening adherence could both accelerate elimination and improve ASR. CONCLUSIONS: The vaccination component of an 'EVEN FASTER' campaign is unlikely to accelerate CC elimination in Norway but may reduce population-level ASR. Alternatively, targeting under- and never-screeners may both eliminate CC faster and lead to greater health benefits compared with vaccination-based interventions we considered.

Architecture and Development Framework for a Web-Based Risk Assessment and Management Platform Developed on WordPress to Address Opioid Overdose.

The number of overdose-related fatalities continues to reach historic levels across Canada, despite ongoing efforts by authorities. To reduce mortality, a clinical trajectory ranging from preventative measures to crisis intervention, skill training to treatment, and risk assessment to risk management needs to be supported. The web-based Risk Assessment and Management Platform (RAMP) was developed to realize this concept and to empower people who use drugs through an integrated tool that allows them to better understand and manage their risk of overdose. This paper outlines the architecture and development of RAMP, which is built on the WordPress platform. WordPress components are mapped onto a 3-tier architecture that consists of presentation, application, and database layers. The architecture facilitates the development of a modular software that includes several features that are independent in functionality but interact with each other in an integrated platform. The relatively low coupling and high coherence of the features may reduce the cost of maintenance and increase flexibility of future developments. RAMP's architecture comprises a user interface, conceptual framework, and backend layers. The RAMP front end effectively uses some of the WordPress' features such as HTML5, CSS, and JavaScript to create a mobile, friendly, and scalable user interface. The RAMP backend uses several standard and custom WordPress plug-ins to support risk assessment and monitoring, with the goal of mitigating the impacts and eliminating risks together. A rule-based decision support system has been hard-coded to suggest relevant modules and goals to complement each user's lifestyle and goals based on their risk assessment. Finally, the backend uses the MySQL database management system and communicates with the RAMP framework layer via the data access layer to facilitate a timely and secure handling of information. Overall, RAMP is a modular system developed to identify and manage the risk of opioid overdose in the population of people who use drugs. Its modular design uses the WordPress architecture to efficiently communicate between layers and provide a base for external plug-ins. There is potential for the current system to adopt and address other related fields such as suicide, anxiety, and trauma. Broader implementation will support this concept and lead to the next level of functionality.

Long-Term Outcome of Proximal Gastrectomy for Upper-Third Advanced Gastric and Siewert Type II Esophagogastric Junction Cancer Compared With Total Gastrectomy: A Propensity Score-Matched Analysis.

BACKGROUND: This study aimed to investigate the oncologic long-term safety of proximal gastrectomy for upper-third advanced gastric cancer (AGC) and Siewert type II esophagogastric junction (EGJ) cancer. METHODS: The study enrolled patients who underwent proximal gastrectomy (PG) or total gastrectomy (TG) with standard lymph node (LN) dissection for pathologically proven upper-third AGC and EGJ cancers between January 2007 and December 2018. Propensity score-matching with a 1:1 ratio was performed to reduce the influence of confounding variables such as age, sex, tumor size, T stage, N stage, and tumor-node-metastasis (TNM) stage. Kaplan-Meier survival analysis was performed to analyze oncologic outcome. The prognostic factors of recurrence-free survival (RFS) were analyzed using the Cox proportional hazard analysis. RESULTS: Of the 713 enrolled patients in this study, 60 received PG and 653 received TG. Propensity score-matching yielded 60 patients for each group. The overall survival rates were 61.7 % in the PG group and 68.3 % in the TG group (p = 0.676). The RFS was 86.7 % in the PG group and 83.3 % in the TG group (p = 0.634). The PG group showed eight recurrences (1 anastomosis site, 1 paraaortic LN, 1 liver, 1 spleen, 1 lung, 1 splenic hilar LN, and 2 remnant stomachs). In the multivariate analysis, the operation method was not identified as a prognostic factor of tumor recurrence. CONCLUSION: The patients who underwent PG had a long-term oncologic outcome similar to that for the patients who underwent TG for upper-third AGC and EGJ cancer.

Ubiquitin ligase RNF20 coordinates sequential adipose thermogenesis with brown and beige fat-specific substrates.

In mammals, brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) execute sequential thermogenesis to maintain body temperature during cold stimuli. BAT rapidly generates heat through brown adipocyte activation, and further iWAT gradually stimulates beige fat cell differentiation upon prolonged cold challenges. However, fat depot-specific regulatory mechanisms for thermogenic activation of two fat depots are poorly understood. Here, we demonstrate that E3 ubiquitin ligase RNF20 orchestrates adipose thermogenesis with BAT- and iWAT-specific substrates. Upon cold stimuli, BAT RNF20 is rapidly downregulated, resulting in GABPα protein elevation by controlling protein stability, which stimulates thermogenic gene expression. Accordingly, BAT-specific Rnf20 suppression potentiates BAT thermogenic activity via GABPα upregulation. Moreover, upon prolonged cold stimuli, iWAT RNF20 is gradually upregulated to promote de novo beige adipogenesis. Mechanistically, iWAT RNF20 mediates NCoR1 protein degradation, rather than GABPα, to activate PPARγ. Together, current findings propose fat depot-specific regulatory mechanisms for temporal activation of adipose thermogenesis.

Acute, Treatment-Naïve Branch Retinal Vein Occlusion in Younger Individuals: Risk Factors and Clinical Outcomes.

Purpose: To compare the risk factors and clinical outcomes in patients younger than 50 years with acute, treatment-naïve branch retinal vein occlusion (BRVO) with outcomes in patients 50 years or older. Methods: Patients diagnosed with acute, treatment-naïve BRVO at Duke Eye Center over a 9.5-year period who had BRVO with onset 3 months or less before presentation, BRVO with macular involvement, and 12 months or more of follow-up were included. Demographic data, presenting clinical features, risk factors, treatment patterns, and clinical outcomes were extracted during a retrospective review of medical records. Results: Of 302 patients identified, 23 were younger than 50 years (younger group) and 279 were 50 years or older (older group). Compared with older patients, younger patients had similar rates of hypertension (P = .275), diabetes mellitus (P = 1.000), smokers (P = .787), and open-angle glaucoma (P = .628). The younger group had a lower rate of hyperlipidemia than the older group (35% vs 59%) (P = .028). The 2 groups had similar presenting logMAR visual acuities (VAs) in the BRVO eye (P = .131). At the final follow-up, younger patients had significantly better logMAR VA in the BRVO-affected eye than older patients (mean 0.51 ± 0.65 vs 1.01 ± 1.20) (P = .016). The 2 groups had similar treatment burdens at 1 year (P = .516) and at the final follow-up (P = .782). Conclusions: Younger patients with acute, treatment-naïve BRVO have similar risk factors and treatment patterns as older patients, except for a lower rate of hyperlipidemia. Younger patients with BRVO may have similar presenting VA as older BRVO patients but better final VA, suggesting that age may be a potential prognostic factor.

Transcutaneous retrobulbar amphotericin B for rhino-orbital-cerebral mucormycosis: a multi-center retrospective comparative study.

PURPOSE: To assess whether transcutaneous retrobulbar amphotericin B injections (TRAMB) reduce exenteration rate without increasing mortality in rhino-orbital-cerebral mucormycosis (ROCM). METHODS: In this retrospective case-control study, 46 patients (51 eyes) with biopsy-proven ROCM were evaluated at 9 tertiary care institutions from 1998 to 2021. Patients were stratified by radiographic evidence of local orbital versus extensive involvement at presentation. Extensive involvement was defined by MRI or CT evidence of abnormal or loss of contrast enhancement of the orbital apex with or without cavernous sinus, bilateral orbital, or intracranial extension. Cases (+TRAMB) received TRAMB as adjunctive therapy while controls (-TRAMB) did not. Patient survival, globe survival, and vision/motility loss were compared between +TRAMB and -TRAMB groups. A generalized linear mixed effects model including demographic and clinical covariates was used to evaluate the impact of TRAMB on orbital exenteration and disease-specific mortality. RESULTS: Among eyes with local orbital involvement, exenteration was significantly lower in the +TRAMB group (1/8) versus -TRAMB (8/14) (p = 0.04). No significant difference in mortality was observed between the ±TRAMB groups. Among eyes with extensive involvement, there was no significant difference in exenteration or mortality rates between the ±TRAMB groups. Across all eyes, the number of TRAMB injections correlated with a statistically significant decreased rate of exenteration (p = 0.048); there was no correlation with mortality. CONCLUSIONS: Patients with ROCM with local orbital involvement treated with adjunctive TRAMB demonstrated a lower exenteration rate and no increased risk of mortality. For extensive involvement, adjunctive TRAMB does not improve or worsen these outcomes.

Cost-effectiveness of primary human papillomavirus triage approaches among vaccinated women in Norway: A model-based analysis.

As Norway considers revising triage approaches following their first adolescent cohort with human papillomavirus (HPV) vaccination entering the cervical cancer screening program, we analyzed the health impact and cost-effectiveness of alternative primary HPV triage approaches for women initiating cervical cancer screening in 2023. We used a multimodeling approach that captured HPV transmission and cervical carcinogenesis to evaluate the health benefits, harms and cost-effectiveness of alternative extended genotyping and age-based triage strategies under five-yearly primary HPV testing (including the status-quo screening strategy in Norway) for women born in 1998 (ie, age 25 in 2023). We examined 35 strategies that varied alternative groupings of high-risk HPV genotypes ("high-risk" genotypes; "medium-risk" genotypes or "intermediate-risk" genotypes), number and types of HPV included in each group, management of HPV-positive women to direct colposcopy or active surveillance, wait time for re-testing and age at which the HPV triage algorithm switched from less to more intensive strategies. Given the range of benchmarks for severity-specific cost-effectiveness thresholds in Norway, we found that the preferred strategy for vaccinated women aged 25 years in 2023 involved an age-based switch from a less to more intensive follow-up algorithm at age 30 or 35 years with HPV-16/18 genotypes in the "high-risk" group. The two potentially cost-effective strategies could reduce the number of colposcopies compared to current guidelines and simultaneously improve health benefits. Using age to guide primary HPV triage, paired with selective HPV genotype and follow-up time for re-testing, could improve both the cervical cancer program effectiveness and efficiency.

Academic machine learning researchers' ethical perspectives on algorithm development for health care: a qualitative study.

OBJECTIVES: We set out to describe academic machine learning (ML) researchers' ethical considerations regarding the development of ML tools intended for use in clinical care. MATERIALS AND METHODS: We conducted in-depth, semistructured interviews with a sample of ML researchers in medicine (N = 10) as part of a larger study investigating stakeholders' ethical considerations in the translation of ML tools in medicine. We used a qualitative descriptive design, applying conventional qualitative content analysis in order to allow participant perspectives to emerge directly from the data. RESULTS: Every participant viewed their algorithm development work as holding ethical significance. While participants shared positive attitudes toward continued ML innovation, they described concerns related to data sampling and labeling (eg, limitations to mitigating bias; ensuring the validity and integrity of data), and algorithm training and testing (eg, selecting quantitative targets; assessing reproducibility). Participants perceived a need to increase interdisciplinary training across stakeholders and to envision more coordinated and embedded approaches to addressing ethics issues. DISCUSSION AND CONCLUSION: Participants described key areas where increased support for ethics may be needed; technical challenges affecting clinical acceptability; and standards related to scientific integrity, beneficence, and justice that may be higher in medicine compared to other industries engaged in ML innovation. Our results help shed light on the perspectives of ML researchers in medicine regarding the range of ethical issues they encounter or anticipate in their work, including areas where more attention may be needed to support the successful development and integration of medical ML tools.

A preliminary randomized controlled trial of repetitive transcranial magnetic stimulation applied to the left dorsolateral prefrontal cortex in treatment seeking participants with cannabis use disorder.

BACKGROUND: Cannabis use disorder (CUD) is a common and consequential disorder. When applied to the dorsolateral prefrontal cortex (DLPFC), repetitive transcranial magnetic stimulation (rTMS) reduces craving across substance use disorders and may have therapeutic clinical effects when applied in serial-sessions. The present study sought to preliminarily determine whether serial-sessions of rTMS applied to the DLPFC had a therapeutic effect in CUD. METHODS: This study was a two-site, phase-2, double-blind, randomized-controlled-trial. Seventy-two treatment-seeking participants (37.5% Women, mean age 30.2±9.9SD) with ≥moderate-CUD were randomized to active or sham rTMS (Beam-F3, 10Hz, 20-total-sessions, two-sessions-per-visit, two-visits-per-week, with cannabis cues) while undergoing a three-session motivational enhancement therapy intervention. The primary outcome was the change in craving between pre- and post- treatment (Marijuana Craving Questionnaire Short-Form-MCQ-SF). Secondary outcomes included the number of weeks of abstinence and the number of days-per-week of cannabis use during 4-weeks of follow-up. RESULTS: There were no significant differences in craving between conditions. Participants who received active-rTMS reported numerically, but not significantly, more weeks of abstinence in the follow-up period than those who received sham-rTMS (15.5%-Active; 9.3%-Sham; rate ratio = 1.66 [95% CI: 0.84, 3.28]; p=0.14). Participants who received active-rTMS reported fewer days-per-week of cannabis use over the final two-weeks of the follow-up period than those receiving sham-rTMS (Active vs. Sham: -0.72; Z=-2.33, p=0.02). CONCLUSIONS: This trial suggests rTMS is safe and feasible in individuals with CUD and may have a therapeutic effect on frequency of cannabis use, though further study is needed with additional rTMS-sessions and a longer follow-up period.

Massive contractions of myotonic dystrophy type 2-associated CCTG tetranucleotide repeats occur via double-strand break repair with distinct requirements for DNA helicases.

Myotonic dystrophy type 2 (DM2) is a genetic disease caused by expanded CCTG DNA repeats in the first intron of CNBP. The number of CCTG repeats in DM2 patients ranges from 75 to 11,000, yet little is known about the molecular mechanisms responsible for repeat expansions or contractions. We developed an experimental system in Saccharomyces cerevisiae that enables the selection of large-scale contractions of (CCTG)100 within the intron of a reporter gene and subsequent genetic analysis. Contractions exceeded 80 repeat units, causing the final repetitive tract to be well below the threshold for disease. We found that Rad51 and Rad52 are involved in these massive contractions, indicating a mechanism that uses homologous recombination. Srs2 helicase was shown previously to stabilize CTG, CAG, and CGG repeats. Loss of Srs2 did not significantly affect CCTG contraction rates in unperturbed conditions. In contrast, loss of the RecQ helicase Sgs1 resulted in a 6-fold decrease in contraction rate with specific evidence that helicase activity is required for large-scale contractions. Using a genetic assay to evaluate chromosome arm loss, we determined that CCTG and reverse complementary CAGG repeats elevate the rate of chromosomal fragility compared to a short-track control. Overall, our results demonstrate that the genetic control of CCTG repeat contractions is notably distinct among disease-causing microsatellite repeat sequences.

Contextual Factors Influencing the Implementation of a Multifaceted Intervention to Improve Teamwork and Quality for Hospitalized Patients: A Multisite Qualitative Comparative Case Study.

BACKGROUND: Many hospitals have begun to implement models that combine interventions to redesign care for medical patients. These models include localization of physicians to specific units, nurse-physician co-leadership, and interprofessional rounds. Understanding contextual factors, the circumstances surrounding an implementation effort that influence its success, is essential to provide guidance to leaders implementing similar models of care. METHODS: A multisite qualitative comparative case study was conducted with four hospitals in the REdesigning SystEms to Improve Teamwork and Quality for Hospitalized Patients (RESET) study. Researchers conducted observations and semistructured interviews with 40 health care professionals and four implementation mentors. Researchers used inductive qualitative content analysis, reviewed fidelity of implementation trends, and performed cross-case analysis to identify contextual factors and their influence on implementation. RESULTS: Four contextual factors were associated with implementation success: (1) senior hospital leader involvement and organizational support; (2) alignment of RESET with organizational, hospital, and professional group priorities; (3) site leaders' engagement in RESET and relationship with one another; and (4) perceptions of need and intervention benefits among professionals. Implementation was optimal when senior leadership was stable and tangibly involved; organizational, hospital, and group goals were aligned; site leaders were committed and collaborated well; and nurses and physicians perceived a need for and benefits from the interventions. CONCLUSION: Four interrelated contextual factors are associated with the implementation of combined interventions to redesign care for hospitalized medical patients. Hospital leaders should consider these findings prior to implementing similar interventions and be prepared to address challenges related to these factors during implementation.

2019 ASCCP Risk-Based Management Consensus Guidelines: Updates Through 2023.

ABSTRACT: This Research Letter summarizes all updates to the 2019 Guidelines through September 2023, including: endorsement of the 2021 Opportunistic Infections guidelines for HIV+ or immunosuppressed patients; clarification of use of human papillomavirus testing alone for patients undergoing observation for cervical intraepithelial neoplasia 2; revision of unsatisfactory cytology management; clarification that 2012 guidelines should be followed for patients aged 25 years and older screened with cytology only; management of patients for whom colposcopy was recommended but not completed; clarification that after treatment for cervical intraepithelial neoplasia 2+, 3 negative human papillomavirus tests or cotests at 6, 18, and 30 months are recommended before the patient can return to a 3-year testing interval; and clarification of postcolposcopy management of minimally abnormal results.