Strategies and Challenges of a Safe Fireplace Program in Rural Kenya: A Qualitative Study.

There is a lack of information on effective burn prevention strategies. The objective of this study was to examine a safe fireplace program, as a method of burn prevention, in a resource-limited setting. We conducted a qualitative, phenomenological study at a community health and development program for a rural population in Kenya. Semi-structured, in-depth interviews were conducted with a purposive sample of community health workers involved with the safe fireplace program. Data were reviewed iteratively and coded independently by two researchers using NVivo 12. The study included five participants. Reflections from participants fell into three main domains: (1) effective methods of education, (2) strategies to incorporate stakeholders, and (3) implementation challenges. The results of this study emphasize the importance of community engagement in implementing a successful burn injury prevention program in a resource-limited setting. The participants involved in this study reported that rather than focusing on resources outside the community, effective methods of education and strategies for incorporating stakeholders depended on involving peers and community leaders. The challenges to the program were similarly specific to community concerns about resources and maintenance. These findings provide information to guide future community health programs in creating successful models for burn prevention strategies in resource-limited areas.

The impact of civil commitment laws for substance use disorder on opioid overdose deaths.

Objective: Our study analyzed the impact of civil commitment (CC) laws for substance use disorder (SUD) on opioid overdose death rates (OODR) in the U.S. from 2010-21. Methods: We used a retrospective study design using the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) dataset to analyze overdose death rates from any opioid during 2010-21 using ICD-10 codes. We used t-tests and two-way ANOVA to compare the OODR between the U.S. states with the law as compared to those without by using GraphPad Prism 10.0. Results: We found no significant difference in the annual mean age-adjusted OODR from 2010-21 between U.S. states with and without CC SUD laws. During the pre-COVID era (2010-19), the presence or absence of CC SUD law had no difference in age-adjusted OODR. However, in the post-COVID era (2020-21), there was a significant increase in OODR in states with a CC SUD law compared to states without the law (p = 0.032). We also found that OODR increased at a faster rate post-COVID among both the states with CC SUD laws (p < 0.001) and the states without the law (p = 0.019). Conclusion: We found higher age-adjusted OODR in states with a CC SUD law which could be due to the laws being enacted in response to the opioid crisis or physicians' opposition to or unawareness of the law's existence leading to underutilization. Recent enactment of CC SUD law(s), a lack of a central database for recording relapse rates, and disparities in opioid overdose rate reductions uncovers multiple variables potentially influencing OODR. Thus, further investigation is needed to analyze the factors influencing OODRs and long-term effects of the CC SUD laws.

MARS an improved de novo peptide candidate selection method for non-canonical antigen target discovery in cancer.

Understanding the nature and extent of non-canonical human leukocyte antigen (HLA) presentation in tumour cells is a priority for target antigen discovery for the development of next generation immunotherapies in cancer. We here employ a de novo mass spectrometric sequencing approach with a refined, MHC-centric analysis strategy to detect non-canonical MHC-associated peptides specific to cancer without any prior knowledge of the target sequence from genomic or RNA sequencing data. Our strategy integrates MHC binding rank, Average local confidence scores, and peptide Retention time prediction for improved de novo candidate Selection; culminating in the machine learning model MARS. We benchmark our model on a large synthetic peptide library dataset and reanalysis of a published dataset of high-quality non-canonical MHC-associated peptide identifications in human cancer. We achieve almost 2-fold improvement for high quality spectral assignments in comparison to de novo sequencing alone with an estimated accuracy of above 85.7% when integrated with a stepwise peptide sequence mapping strategy. Finally, we utilize MARS to detect and validate lncRNA-derived peptides in human cervical tumour resections, demonstrating its suitability to discover novel, immunogenic, non-canonical peptide sequences in primary tumour tissue.

Improving multimodal physical function in adults with heterogeneous chronic pain; Protocol for a multisite feasibility RCT.

BACKGROUND: Chronic pain is associated with substantial impairment in physical function, which has been identified as a top concern among persons with pain. GetActive-Fitbit, a mind-body activity program, is feasible, acceptable, and associated with improvement in physical function among primarily White, sedentary individuals with pain. In preparation for a multisite efficacy trial, we must examine feasibility across multiple sites with diverse patient populations. Here we describe the protocol of a multisite, feasibility RCT comparing GetActive-Fitbit with a time- and attention-matched educational comparison (Healthy Living for Pain). We aim to 1) test multisite fidelity of clinician training; 2) evaluate multisite feasibility benchmarks, including recruitment of chronic pain patients taking <5000 steps/day and racial and ethnic minorities; and 3) optimize fidelity and study protocol in preparation for a future multisite efficacy trial. METHODS: Clinician training fidelity was assessed via roleplays and mock group sessions. Feasibility (i.e., recruitment, acceptability, credibility, adherence, satisfaction), multimodal physical function (e.g., self-report, 6-Minute Walk Test, step-count), and other psychosocial outcomes are assessed at baseline, posttest, and 6 months. Protocol optimization will be assessed using exit interviews and cross-site meetings. RESULTS: The trial is ongoing. Clinician training is complete. 87 participants have been recruited. 54 completed baseline assessments and randomization, 44 are mid-intervention, and 9 have completed the intervention and posttest. CONCLUSIONS: This study addresses the critical need for feasible, acceptable mind-body-activity interventions for chronic pain that follow evidence-based guidelines and improve all aspects of physical function across diverse populations. Results will inform a future fully-powered multisite efficacy trial. CLINICAL TRIAL REGISTRATION: NCT05700383.

Gender Disparities in Complications, Costs, and Mortality After Emergency Gastrointestinal Surgery in Kenya.

INTRODUCTION: Little is known about the impact of gender on emergency surgery within Kenya. Therefore, we aimed to investigate the association of gender on outcomes of postoperative complications, health care costs, and mortality. METHODS: We evaluated an established cohort of patients undergoing emergency gastrointestinal surgery in rural Kenya between January 1st, 2016 and June 30th, 2019. Utilizing logistic regression, we examined the association between self-reported patient gender and the outcomes of postoperative complications and mortality. A generalized linear model was created for total hospital costs, inflation-adjusted in international dollars purchasing power parity, to examine the impact of gender. Confounding factors were controlled by Africa Surgical Outcomes Study Surgical Risk Score. RESULTS: Among 484 patients reviewed, 149 (30.8%) were women. 165 (34.1%) patients developed complications, with women experiencing more than men (40.9% versus 31.0%; P = 0.03) and longer hospital stays (median 6 days (4-9) versus 5 (4-7); P = 0.02). After controlling for Africa Surgical Outcomes Study Surgical Risk Score, odds of developing complications for women were 1.67 (95% confidence interval: 1.09-2.55; P = 0.019) times higher than men, and the odds of death were 2.38 (95% confidence interval: 1.12-5.09; P = 0.025) times greater for women than men, despite similar failure-to-rescue rates and intensive care unit utilization. Total hospital costs were increased for women by 531 international dollars purchasing power parity (117-946; P = 0.012) when compared to men, attributed to longer lengths of stay. CONCLUSIONS: These findings demonstrate that a discrepancy exists between men and women undergoing emergency gastrointestinal surgery in our setting. Further exploration of the underlying causes of this inequity is necessary for quality improvement for women in rural Kenya.

Interferon-α promotes neo-antigen formation and preferential HLA-B-restricted antigen presentation in pancreatic ß-cells.

Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but its effect on the repertoire of HLA Class I (HLA-I)-bound peptides presented by pancreatic ß-cells is unknown. Using immunopeptidomics, we characterized the peptide/HLA-I presentation in in-vitro resting and IFN-α-exposed ß-cells. IFN-α increased HLA-I expression and peptide presentation, including neo-sequences derived from alternative mRNA splicing, post-translational modifications - notably glutathionylation - and protein cis-splicing. This antigenic landscape relied on processing by both the constitutive and immune proteasome. The resting ß-cell immunopeptidome was dominated by HLA-A-restricted ligands. However, IFN-α only marginally upregulated HLA-A and largely favored HLA-B, translating into a major increase in HLA-B-restricted peptides and into an increased activation of HLA-B-restricted vs. HLA-A-restricted CD8+ T-cells. A preferential HLA-B hyper-expression was also observed in the islets of T1D vs. non-diabetic donors, and we identified islet-infiltrating CD8+ T-cells from T1D donors reactive to HLA-B-restricted granule peptides. Thus, the inflammatory milieu of insulitis may skew the autoimmune response toward epitopes presented by HLA-B, hence recruiting a distinct T-cell repertoire that may be relevant to T1D pathogenesis.

Addressing the Chronic Pain-Early Cognitive Decline Comorbidity Among Older Adults: Protocol for the Active Brains Remote Efficacy Trial.

BACKGROUND: Chronic pain and early cognitive decline, which are costly to treat and highly prevalent among older adults, commonly co-occur, exacerbate one another over time, and can accelerate the development and progression of Alzheimer disease and related dementias. We developed the first mind-body activity program (Active Brains [AB]) tailored to the needs of older adults with chronic pain and early cognitive decline. Results from our previous study strongly supported the feasibility of conducting AB remotely and provided evidence for improvements in outcomes. OBJECTIVE: We are conducting a single-blinded, National Institutes of Health stage-2, randomized clinical trial to establish the efficacy of AB versus a time-matched and dose-matched education control (Health Enhancement Program [HEP]) in improving self-reported and objective outcomes of physical, cognitive, and emotional functions in 260 participants. The methodology described in this paper was informed by the lessons learned from the first year of the trial. METHODS: Participants are identified and recruited through multidisciplinary clinician-referred individuals (eg, pain psychologists and geriatricians), the Rally Research platform, social media, and community partnerships. Interested participants complete eligibility screening and electronic informed consent. Baseline assessments include self-report, performance-based measures (eg, 6-min walk test) and objective measures (eg, Repeatable Battery for the Assessment of Neuropsychological Status). Participants are mailed a wrist-worn ActiGraph device (ActiGraph LLC) to passively monitor objective function (eg, steps) during the week between the baseline assessment and the beginning of the programs, which they continue to wear throughout the programs. After baseline assessments, participants are randomized to either AB or HEP and complete 8 weekly, remote, group sessions with a Massachusetts General Hospital psychologist. The AB group receives a Fitbit (Fitbit Inc) to help reinforce increased activity. Assessments are repeated after the intervention and at the 6-month follow-up. Coprimary outcomes include multimodal physical function (self-report, performance based, and objective). Secondary outcomes are cognitive function (self-report and objective), emotional function, and pain. RESULTS: We began recruitment in July 2022 and recruited 37 participants across 4 cohorts. Of them, all (n=37, 100%) have completed the baseline assessment, 26 (70%) have completed the posttest assessment, and 9 (24%) are actively enrolled in the intervention (total dropout: n=2, 5%). In the three cohorts (26/37, 70%) that have completed the AB or HEP, 26 (100%) participants completed all 8 group sessions (including minimal makeups), and watch adherence (1937/2072, 93.48%, average across ActiGraph and Fitbit devices) has been excellent. The fourth cohort is ongoing (9/37, 24%), and we plan to complete enrollment by March 2026. CONCLUSIONS: We aim to establish the efficacy of the AB program over a time-matched and dose-matched control in a live video-based trial and test the mechanisms through theoretically driven mediators and moderators. Findings will inform the development of a future multisite effectiveness-implementation trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05373745; https://classic.clinicaltrials.gov/ct2/show/NCT05373745. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47319.

A Live Video Dyadic Resiliency Intervention to Prevent Chronic Emotional Distress Early After Dementia Diagnoses: Protocol for a Dyadic Mixed Methods Study.

BACKGROUND: By 2030, approximately 75 million adults will be living with Alzheimer disease and related dementias (ADRDs). ADRDs produce cognitive, emotional, and behavioral changes for persons living with dementia that undermine independence and produce considerable stressors for persons living with dementia and their spousal care-partners-together called a "dyad." Clinically elevated emotional distress (ie, depression and anxiety symptoms) is common for both dyad members after ADRD diagnosis, which can become chronic and negatively impact relationship functioning, health, quality of life, and collaborative management of progressive symptoms. OBJECTIVE: This study is part of a larger study that aims to develop, adapt, and establish the feasibility of Resilient Together for Alzheimer Disease and Related Dementias (RT-ADRD), a novel dyadic skills-based intervention aimed at preventing chronic emotional distress. This study aims to gather comprehensive information to develop the first iteration of RT-ADRD and inform a subsequent open pilot. Here, we describe the proposed study design and procedures. METHODS: All procedures will be conducted virtually (via phone and Zoom) to minimize participant burden and gather information regarding feasibility and best practices surrounding virtual procedures for older adults. We will recruit dyads (up to n=20) from Mount Sinai Hospital (MSH) clinics within 1 month of ADRD diagnosis. Dyads will be self-referred or referred by their treating neurologists and complete screening to assess emotional distress and capacity to consent to participate in the study. Consenting dyads will then participate in a 60-minute qualitative interview using an interview guide designed to assess common challenges, unmet needs, and support preferences and to gather feedback on the proposed RT-ADRD intervention content and design. Each dyad member will then have the opportunity to participate in an optional individual interview to gather additional feedback. Finally, each dyad member will complete a brief quantitative survey remotely (by phone, tablet, or computer) via a secure platform to assess feasibility of assessment and gather preliminary data to explore associations between proposed mechanisms of change and secondary outcomes. We will conduct preliminary explorations of feasibility markers, including recruitment, screening, live video interviews, quantitative data collection, and mixed methods analyses. RESULTS: This study has been approved by the MSH Institutional Review Board. We anticipate that the study will be completed by late 2023. CONCLUSIONS: We will use results from this study to develop the first live video telehealth dyadic resiliency intervention focused on the prevention of chronic emotional distress in couples shortly after ADRD diagnoses. Our study will allow us to gather comprehensive information from dyads on important factors to address in an early prevention-focused intervention and to explore feasibility of study procedures to inform future open pilot and pilot feasibility randomized control trial investigations of RT-ADRD. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/45532.

Implementation of a Smartphone-Based Platform for Operative Feedback at Tenwek Hospital in Kenya: A Mixed Methods Study.

BACKGROUND: The SIMPL operative feedback tool is used in many U.S. surgical residency programs. However, the challenges of implementation and benefits of the web-based platform in low- and middle-income countries are unknown. The aim of this study was to evaluate implementation of SIMPL in a general surgery residency training program in Kenya. METHODS: SIMPL was pilot tested at Tenwek Hospital from January through December 2021. Participant perspectives of SIMPL were elicited through a survey and semi-structured interviews. Descriptive statistics were used to analyze survey data. Inductive qualitative content analysis of interview responses was performed by two independent researchers. RESULTS: Fourteen residents and six faculty (100% response rate) were included in the study and completed over 600 operative assessments. All respondents reported numerical evaluations and dictated feedback were useful. Respondents felt that SIMPL was easy to use, improved quality and frequency of feedback, helped refine surgical skills, and increased resident autonomy. Barriers to use included participants forgetting to complete evaluations, junior residents not submitting evaluations when minimally involved in cases, and technological challenges. Suggestions for improvement included expansion of SIMPL to surgical subspecialties and allowing senior residents to provide feedback to juniors. All respondents wanted to continue using SIMPL, and 90% recommended use at other programs. CONCLUSION: Residents and faculty at Tenwek Hospital believed SIMPL were a positive addition to their training program. There were a few barriers to use and suggestions for improvement specific to the training environment in Kenya, but this study demonstrates it is feasible to use SIMPL in settings outside the U.S. with the appropriate resources.

Operative Case Volumes and Variation for General Surgery Training in East, Central, and Southern Africa.

BACKGROUND: Operative experience is a necessary part of surgical training. The College of Surgeons of East, Central, and Southern Africa (COSECSA), which oversees general surgery training programs in the region, has implemented guidelines for the minimum necessary case volumes upon completion of two (Membership) and five (Fellowship) years of surgical training. We aimed to review trainee experience to determine whether guidelines are being met and examine the variation of cases between countries. METHODS: Operative procedures were categorized from a cohort of COSECSA general surgery trainees and compared to the guideline minimum case volumes for Membership and Fellowship levels. The primary and secondary outcomes were total observed case volumes and cases within defined categories. Variations by country and development indices were explored. RESULTS: One hundred ninety-four trainees performed 69,283 unique procedures related to general surgery training. The review included 70 accredited hospitals and sixteen countries within Africa. Eighty percent of MCS trainees met the guideline minimum of 200 overall cases; however, numerous trainees did not meet the guideline minimum for each procedure. All FCS trainees met the volume target for total cases and orthopedics; however, many did not meet the guideline minimums for other categories, especially breast, head and neck, urology, and vascular surgery. The operative experience of trainees varied significantly by location and national income level. CONCLUSIONS: Surgical trainees in East, Central, and Southern Africa have diverse operative training experience. Most trainees fulfill the overall case volume requirements; however, further exploration of how to meet the demands of specific categories and procedures is necessary.

Fractal patterns in the parameter space of a bistable Duffing oscillator.

We study the dissipative bistable Duffing oscillator with equal energy wells and observe fractal patterns in the parameter space of driving frequency, forcing amplitude, and damping ratio. Our numerical investigation reveals the Hausdorff fractal dimension of the boundaries that separate the oscillator's intrawell and interwell behaviors. Furthermore, we categorize the interwell behaviors as three steady-state types: switching, reverting, and vacillating. While fractal patterns in the phase space are well known and heavily studied, our results point to another research direction about fractal patterns in the parameter space. Another implication of this study is that the vibration of a continuous bistable system modeled using a single-mode approximation also manifests fractal patterns in the parameter space. In addition, our findings can guide the design of next-generation bistable and multistable mechanical metamaterials.

Effects of physical exercise, LEGO, and Minecraft activities on anxiety in underserved children with autism: Study design and methodological strategies.

Anxiety is a common comorbidity for individuals with ASD, and there is some preliminary data about the efficacy of physical exercise to alleviate anxiety. However, we are not aware of any studies that have compared the effects of a physical exercise program on anxiety in underserved children with ASD using a randomized controlled research design. This paper describes a method to evaluate and compare the efficacy of an 8-week physical exercise intervention with a sedentary play intervention to alleviate anxiety in young children with autism spectrum disorders (ASD) from underserved backgrounds. We assessed anxiety and its physical symptoms using the parent-rated Child Behavior Checklist DSM-5 anxiety (CBCL DSM-5) subscale, the child-rated Screen for Childhood Anxiety Related Emotional Disorder (SCARED), the parent-rated Child's Sleep Habits Questionnaire (CSHQ), and salivary cortisol. We also utilized the Physical Activity Questionnaire for Older Children (PAQ-C) to assess physical activity level and identify compounds. Unique components of this study include: •Implementation of novel physical exercise and sedentary play interventions that have been designed for children with ASD.•Recruitment of predominantly underserved and non-English speaking families.

Trainee autonomy and surgical outcomes after emergency gastrointestinal surgery.

BACKGROUND: Operative meaningful trainee autonomy is an essential component of surgical training. Reduced trainee autonomy is frequently attributed to patient safety concerns, but this has not been examined within Kenya. We aimed to assess whether meaningful trainee autonomy was associated with a change in patient outcomes. METHODS: We investigated whether meaningful trainee autonomy was associated with a change in severe postoperative complications and all-cause in-hospital mortality in a previously described cohort undergoing emergency gastrointestinal operations. Each operation was reviewed to determine the presence of meaningful autonomy, defined as "supervision only" from faculty. Comparisons were made between faculty-led cases and cases with meaningful trainee autonomy. Multilevel logistic regression models were created for the outcomes of mortality and complications with the exposure of meaningful trainee autonomy, accounting for fixed effects of the Africa Surgical Outcomes Study Risk Score and random effects of discharge diagnoses. RESULTS: After excluding laparoscopy (N = 28) and missing data (N = 3), 451 operations were studied, and 343 (76.1%) had meaningful trainee autonomy. Faculty were more involved in operations with older age, cancer, prior complications, and higher risk scores. On unadjusted analysis, meaningful trainee autonomy was associated with mortality odds of 0.32 (95% confidence interval: 0.17-0.58) compared with faculty-led operations. Similarly, the odds of developing complications were 0.52 (95% confidence interval: 0.32-0.84) with meaningful trainee autonomy compared with faculty-led operations. When adjusting for Africa Surgical Outcomes Study Score and clustering discharge diagnoses, the odds of mortality (odds ratio 0.58; 95% confidence interval: 0.27-1.2) and complication (odds ratio 0.83; 95% confidence interval: 0.47-1.5) were not significant. CONCLUSION: Our findings support that increasing trainee autonomy does not change patient outcomes in selected emergency gastrointestinal operations. Further, trainees and faculty appropriately discern patients at higher risk of complications and mortality, and the selective granting of trainee autonomy does not affect patient safety.

Focus Group Study of Medical Stakeholders to Inform the Development of Resilient Together for Dementia: Protocol for a Postdiagnosis Live Video Dyadic Resiliency Intervention.

BACKGROUND: Alzheimer disease and related dementias (ADRD) are increasingly common conditions that disrupt the lives of persons living with dementia and their spousal care partners. At the time of ADRD diagnoses, many couples experience challenges that produce emotional distress and relationship strain. At present, there are no interventions to address these challenges early after diagnoses to promote positive adjustment. OBJECTIVE: The study protocol described here is part of the first phase of a larger program of research that aims to develop, adapt, and establish the feasibility of Resilient Together for Dementia (RT-ADRD), a novel dyadic skills-based intervention to be delivered over live video early after diagnosis, with the goal of preventing chronic emotional distress. This study will elicit and systematically summarize perspectives of ADRD medical stakeholders to inform the procedures (eg, recruitment and screening methods, eligibility, timing of intervention, and intervention delivery) of the first iteration of RT-ADRD prior to pilot-testing. METHODS: We will recruit interdisciplinary medical stakeholders (eg, neurologists, social workers, neuropsychologists, care coordinators, and speech language pathologists) from academic medical center clinics in the departments treating persons living with dementia such as neurology, psychiatry, and geriatric medicine via flyers and word-of-mouth referrals from clinic directors and members of relevant organizations (eg, dementia care collaboratives and Alzheimer disease research centers). The participants will complete electronic screening and consent procedures. Consenting individuals will then participate in a 30- to 60-minute qualitative virtual focus group, held either via telephone or Zoom, using an interview guide designed to assess provider experiences with postdiagnosis clinical care and to gather feedback on the proposed RT-ADRD protocol. The participants will also have the opportunity to participate in an optional exit interview and web-based survey to gather additional feedback. Qualitative data will be analyzed using a hybrid inductive-deductive approach and the framework method for thematic synthesis. We will conduct approximately 6 focus groups with 4-6 individuals in each group (maximum N=30 individuals; until saturation is reached). RESULTS: Data collection began in November 2022 and will continue through June 2023. We anticipate that the study will be completed by late 2023. CONCLUSIONS: The results from this study will inform the procedures of the first live video RT-ADRD dyadic resiliency intervention focused on the prevention of chronic emotional and relational distress in couples shortly after ADRD diagnoses. Our study will allow us to gather comprehensive information from stakeholders on ways to best deliver our early prevention-focused intervention and gain detailed feedback on study procedures prior to further testing. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45533.

Observation-derived 2010-2019 trends in methane emissions and intensities from US oil and gas fields tied to activity metrics.

The United States is the world's largest oil/gas methane emitter according to current national reports. Reducing these emissions is a top priority in the US government's climate action plan. Here, we use a 2010 to 2019 high-resolution inversion of surface and satellite observations of atmospheric methane to quantify emission trends for individual oil/gas production regions in North America and relate them to production and infrastructure. We estimate a mean US oil/gas methane emission of 14.8 (12.4 to 16.5) Tg a-1 for 2010 to 2019, 70% higher than reported by the US Environmental Protection Agency. While emissions in Canada and Mexico decreased over the period, US emissions increased from 2010 to 2014, decreased until 2017, and rose again afterward. Increases were driven by the largest production regions (Permian, Anadarko, Marcellus), while emissions in the smaller production regions generally decreased. Much of the year-to-year emission variability can be explained by oil/gas production rates, active well counts, and new wells drilled, with the 2014 to 2017 decrease driven by reduction in new wells and the 2017 to 2019 surge driven by upswing of production. We find a steady decrease in the oil/gas methane intensity (emission per unit methane gas production) for almost all major US production regions. The mean US methane intensity decreased from 3.7% in 2010 to 2.5% in 2019. If the methane intensity for the oil/gas supply chain continues to decrease at this pace, we may expect a 32% decrease in US oil/gas emissions by 2030 despite projected increases in production.

PSA density does not improve predictive accuracy of the UCSF-CAPRA score.

INTRODUCTION: The University of California, San Francisco Cancer of the Prostate Risk Assessment (CAPRA) score is a validated tool using factors at diagnosis to predict prostate cancer outcomes after radical prostatectomy (RP). This study evaluates whether substitution of prostate-specific antigen (PSA) density for serum PSA improves predictive performance of the clinical CAPRA model. METHODS: Participants were diagnosed in 2000-2019 with stage T1/T2 cancer, underwent RP, with at least a 6-month follow-up. We computed standard CAPRA score using diagnostic age, Gleason grade, percent positive cores, clinical T stage, and serum PSA, and an alternate score using similar variables but substituting PSA density for PSA. We reported CAPRA categories as low (0-2), intermediate (3-5), and high (6-10) risk. Recurrence was defined as two consecutive PSA ≥ 0.2 ng/mL or receipt of salvage treatment. Life table and Kaplan-Meier analysis evaluated recurrence-free survival after prostatectomy. Cox proportional hazards regression models tested associations of standard or alternate CAPRA variables with recurrence risk. Additional models tested associations between standard or alternate CAPRA score with recurrence risk. Cox log-likelihood ratio test (-2 LOG L) assessed model accuracy. RESULTS: A total of 2880 patients had median age 62 years, GG1 30% and GG2 31%, median PSA 6.5, and median PSA density 0.19. Median postoperative follow-up was 45 months. Alternate CAPRA model was associated with shifts in risk scores, with 16% of patients increasing and 7% decreasing (p < 0.01). Recurrence-free survival after RP was 75% at 5 years and 62% at 10 years. Both CAPRA component models were associated with recurrence risk after RP on Cox regression. Covariate fit statistics showed better fit for standard CAPRA model versus alternate (p < 0.01). Standard (hazard ratio [HR]: 1.55; 95% confidence interval [CI]: 1.50-1.61) and alternate (HR: 1.50; 95% CI: 1.44-1.55) CAPRA scores were associated with recurrence risk, with better fit for standard model (p < 0.01). CONCLUSIONS: In a 2880 patient cohort followed for median 45 months after RP, alternate CAPRA model using PSA density was associated with higher biochemical recurrence (BCR) risk, but performed inferior to standard CAPRA at predicting BCR. While PSA density is an established prognostic variable in prediagnostic settings and sub-stratifying low-risk disease, it does not improve BCR model predictive accuracy when applied across a range of cancer risk.

Stability of Prognostic Estimation Using the CAPRA Score Incorporating Imaging-based vs Physical Exam-based Staging.

PURPOSE: Although official T-staging criteria for prostate cancer are based on digital rectal examination findings, providers increasingly rely on transrectal US and MRI to define pragmatic clinical stage to guide management. We assessed the impact of incorporating imaging findings into T-staging on performance of a well-validated prognostic instrument. MATERIALS AND METHODS: Patients who underwent radical prostatectomy for prostate cancer diagnosed between 2000 and 2019 with stage ≤cT3a on both digital rectal examination and imaging (transrectal US/MRI) were included. The University of California, San Francisco CAPRA (Cancer of the Prostate Risk Assessment) score was computed 2 ways: (1) incorporating digital rectal examination-based T stage and (2) incorporating imaging-based T stage. We assessed for risk changes across the 2 methods and associations of CAPRA (by both methods) with biochemical recurrence, using unadjusted and adjusted Cox proportional hazards models. Model discrimination and net benefit were assessed with time-dependent area under the curve and decision curve analysis, respectively. RESULTS: Of 2,222 men included, 377 (17%) increased in CAPRA score with imaging-based staging (P < .01). Digital rectal examination-based (HR 1.54; 95% CI 1.48-1.61) and imaging-based (HR 1.52; 95% CI 1.46-1.58) CAPRA scores were comparably accurate for predicting recurrence with similar discrimination and decision curve analyses. On multivariable Cox regression, positive digital rectal examination at diagnosis (HR 1.29; 95% CI 1.09-1.53) and imaging-based clinical T3/4 disease (HR 1.72; 95% CI 1.43-2.07) were independently associated with biochemical recurrence. CONCLUSIONS: The CAPRA score remains accurate whether determined using imaging-based staging or digital rectal examination-based staging, with relatively minor discrepancies and similar associations with biochemical recurrence. Staging information from either modality can be used in the CAPRA score calculation and still reliably predict risk of biochemical recurrence.

An anesthesia-centered bundle to reduce postoperative pulmonary complications: The PRIME-AIR study protocol.

BACKGROUND: Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality after open abdominal surgery. Optimized perioperative lung expansion may minimize the synergistic factors responsible for the multiple-hit perioperative pulmonary dysfunction. This ongoing study will assess whether an anesthesia-centered bundle focused on perioperative lung expansion results in decreased incidence and severity of PPCs after open abdominal surgery. METHODS: Prospective multicenter randomized controlled pragmatic trial in 750 adult patients with at least moderate risk for PPCs undergoing prolonged (≥2 hour) open abdominal surgery. Participants are randomized to receive either a bundle intervention focused on perioperative lung expansion or usual care. The bundle intervention includes preoperative patient education, intraoperative protective ventilation with individualized positive end-expiratory pressure to maximize respiratory system compliance, optimized neuromuscular blockade and reversal management, and postoperative incentive spirometry and early mobilization. Primary outcome is the distribution of the highest PPC severity by postoperative day 7. Secondary outcomes include the proportion of participants with: PPC grades 1-2 through POD 7; PPC grades 3-4 through POD 7, 30 and 90; intraoperative hypoxemia, rescue recruitment maneuvers, or cardiovascular events; and any major extrapulmonary postoperative complications. Additional secondary and exploratory outcomes include individual PPCs by POD 7, length of postoperative oxygen therapy or other respiratory support, hospital resource use parameters, Patient-Reported Outcomes Measurements (PROMIS®) questionnaires for dyspnea and fatigue collected before and at days 7, 30 and 90 after surgery, and plasma concentrations of lung injury biomarkers (IL6, IL-8, RAGE, CC16, Ang-2) analyzed from samples obtained before, end of, and 24 hours after surgery. DISCUSSION: Participant recruitment for this study started January 2020; results are expected in 2024. At the conclusion of this trial, we will determine if this anesthesia-centered strategy focused on perioperative lung expansion reduces lung morbidity and healthcare utilization after open abdominal surgery. TRIAL REGISTRATION: ClinicalTrial.gov NCT04108130.