Intervention to promote adolescents' communication and engagement in diabetes clinic encounters: A pilot randomized controlled trial.

AIM: To conduct a pilot randomized trial of an intervention to improve adolescent question-asking and provider education during paediatric diabetes visits. METHODS: Adolescents aged 11 to 17 with type 1 diabetes and their parents were enrolled from two urban tertiary paediatric clinics. Adolescents were randomised to the intervention group or control group. Adolescent consultations were audio-recorded, their HbA1c level was recorded, and they completed surveys after three clinic appointments. The intervention group completed a question prompt list and watched a video on a tablet with their parents before meeting their doctor and completed a short evaluation after each visit. RESULTS: Six consultant endocrinologists and ninety-nine adolescents and their parents participated. The intervention increased adolescents' question asking and provider education in diabetes encounters. Total patient question-asking across the 3 consultations and a higher baseline HbA1c at time one was significantly associated with HbA1c at time three. CONCLUSIONS: Question prompt lists and an educational video are useful tools to increase adolescents' question-asking and communication between adolescents and their providers. PRACTICE IMPLICATIONS: Interventions that encourage adolescents' question-asking in healthcare encounters may lead to more meaningful providers-adolescents' communication and tailored education. Interventions to improve professionals' listening, communication and educational skills are also required.

Challenges and Coping Strategies in Transitioning From Caregiving to Widowhood: A Systematic Review.

Ninety-one percent of surviving spouses in the U.S. cared for their spouses before they died. This review explores the challenges of the transition from caregiving to widowhood and different coping strategies used by widowed spousal caregivers. A systematic review of literature on the transition from caregiving to widowhood was conducted using four major academic search engines. Overall, 280 articles were identified, with 22 meeting the inclusion criteria. Challenges for widowed caregivers included experiencing care burden, letting go of the caregiver role, grief, and triggers. Widowed caregivers' coping strategies included social support and services use, filling the time gap, finding spirituality, and engaging in unhealthy behaviors. Future research is needed to determine the efficacy of widowed caregivers' coping strategies. Concerted and collaborative action by health professionals, community organizations, and policymakers is needed to develop programs and other approaches to support widowed caregivers.

Financial train, health behaviors, and psychological well-being of family caregivers of older adults during the COVID-19 pandemic.

Objectives: This study aims to examine the change in financial strain, health behaviors, and psychological well-being of family caregivers of older adults during the COVID-19 pandemic and explore the differences in mental health outcomes by gender, race, and relationship status. Methods: Using the 2020 National Health and Aging Trends Study COVID-19 supplement, our sample included 2026 family caregivers of older adults. Structural equation modeling was conducted. Results: Caregivers with financial strain showed worse mental health than those with no financial strain. Female or adult children caregivers reported significantly less time walking, more financial strain, and a higher level of negative mental health outcomes compared to male or spouse caregivers; non-White caregivers reported greater positive mental health outcomes compared to White caregivers during the pandemic. Discussion: Health professionals should consider the financial and mental health impact of COVID-19 among family caregivers when designing and delivering caregiver support programs. Innovation: This study provides nationally representative estimates of several important health behaviors and health outcomes for caregivers of older adults during and after the COVID-19 pandemic, helping to fill the knowledge gap about the characteristics of caregivers whose health and well-being were most affected by the pandemic.

Post-acute day and night non-invasive respiratory intervention use and outcome: A brief report.

OBJECTIVE: This study aimed to describe daytime and nighttime use and outcome of non-invasive respiratory intervention (NIRI) for infants born prematurely and for children with medical complexity (CMC) during a post-acute care hospital (PACH) admission. METHODS: Thirty-eight initial PACH admissions (October 2018 through September 2020) for premature infants (< 1 year; n = 19) and CMC (> 1 year; n = 19) requiring NIRI during the day and/or at night were retrospectively examined. Measures included: 1) daytime and nighttime NIRI use by type (supplemental oxygen therapy via low-flow nasal cannula or positive airway pressure [PAP] via high-flow nasal cannula, continuous positive airway pressure, or biphasic positive airway pressure at admission and discharge) and 2) daytime and nighttime NIRI outcome-reduction, increase, or no change from admission to discharge. RESULTS: For the total sample (n = 38), daytime vs nighttime NIRI use was significantly different (p < 0.001). At both admission and discharge, supplemental oxygen was the most common NIRI during the day, while PAP was most common at night. From admission to discharge, seven (18%) infants and children had a positive change (reduced NIRI) during the day, while nine (24%) had a positive change at night. At discharge, 11/38 (29%) infants and children required no daytime NIRI, while 4/38 (11%) required no day or night NIRI. CONCLUSION: NIRI use differs between day and night at PACH admission and discharge for CMC. Reductions in NIRI were achieved during the day and at night from PACH admission to discharge for both infants born prematurely and for children with varied congenital, neurological, or cardiac diagnoses.

Is pelvic ultrasound useful in the clinical assessment and management of women with right iliac fossa pain? A single-centre retrospective study.

INTRODUCTION: Acute right iliac fossa (RIF) pain is a common presenting symptom in surgical patients, with a wide range of differentials, particularly in premenopausal females. This study explores ultrasound usage in the management of women aged 16-55 years presenting with RIF pain. METHODS: A total of 1,082 patients who presented to a tertiary hospital over 12 months were included. Data were collected from patients' electronic records, including initial clinical impression, imaging, management, operative findings, histology and subsequent hospital attendances within 6 weeks and within 6 months. RESULTS: Following clinical assessment, 607 (56%) of patients underwent an ultrasound. Of these, 280 (25.9%) patients received no radiological imaging on initial presentation, and 252 (42%) had pathology identified on ultrasound. The most common finding was an ovarian cyst, closely followed by unexplained free pelvic fluid. Of the 607 patients scanned, 29 (4.8%) had an ultrasound diagnosis of appendicitis; 254 of 1,082 (23.5%) patients underwent operative management. Of the 254 patients who had surgery, 179 (70.5%) had preoperative imaging. Of the 29 (11.4%) cases where the intraoperative finding was gynaecological, 15 (51.7%) cases had not had any preoperative imaging. The negative appendicectomy rate was 21.3% (45/211). Of the 45 patients who had a histologically normal appendix, 22 (48.9%) had not had any previous imaging. Ultrasound had a specificity of 78% for diagnosing appendicitis. CONCLUSIONS: In patients who underwent operative management, a negative finding or finding not requiring surgical management was associated with no preoperative imaging. This supports the use of ultrasound scans as an adjunct in a multimodal approach to the assessment of women presenting with RIF pain.

Listening to School Nurses' Voices: A Mixed Methods Study on the Continued Impact of COVID-19 on School Nursing Practice.

School closures in March 2020 due to the COVID-19 pandemic precipitated losses of critical student resources as physical, mental, emotional, and social needs escalated. Identifying the challenges, strategies, and changes in school nurse (SN) practice in Massachusetts during this pandemic is fundamental to understanding how to manage future anticipated pandemics while protecting children, communities, and SNs. The purpose of this mixed-methods descriptive study in the second year of the global pandemic was to (a) listen to SN voices through a novel online survey including the prompts of challenges, strategies, and practice changes and (b) describe the SN experience of COVID-19 response in Massachusetts schools, including identification of intent to leave school nursing. Responses were analyzed using descriptive qualitative analysis (n = 73). The prompts each elicited subthemes that coalesced to a cohesive theme: Finding one's way required the support of others to pave untraversed roads.

In vitro activity of gepotidacin and comparator antimicrobials against isolates of nontuberculous mycobacteria (NTM).

Novel antimicrobials are needed to treat rising nontuberculous mycobacteria (NTM) infections. Using standard broth microdilution methods, 68 NTM isolates were tested against gepotidacin, a new, first-in-class, oral triazaacenaphthylene bacterial topoisomerase inhibitor. MICs varied (0.25 to >64 µg/mL) with the lowest being M. fortuitum complex (0.25-8 µg/mL), M. mucogenicum complex (1-2 µg/mL), M. kansasii (0.25-8 µg/mL), and M. marinum (4-16 µg/mL). Testing greater numbers of some species is suggested to better understand gepotidacin activity against NTM.

Measuring decision aid effectiveness for end-of-life care: A systematic review.

Objective: To systematically review research analyzing the effectiveness of decision aids for end-of-life care, including how researchers specifically measure decision aid success. Methods: We conducted a systematic review synthesizing quantitative, qualitative, and mixed-methods study results using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Four databases were searched through February 18, 2023. Inclusion criteria required articles to evaluate end-of-life care decision aids. The review is registered under PROSPERO (#CRD42023408449). Results: A total of 715 articles were initially identified, with 43 meeting the inclusion criteria. Outcome measures identified included decisional conflict, less aggressive care desired, knowledge improvements, communication improvements, tool satisfaction, patient anxiety and well-being, and less aggressive care action completed. The majority of studies reported positive outcomes especially when the decision aid development included International Patient Decision Aid Standards. Conclusion: Research examining end of life care decision aid use consistently reports positive outcomes. Innovation: This review presents data that can guide the next generation of decision aids for end-of-life care, namely using the International Patient Decision Aid Standards in developing tools and showing which tools are effective for helping to prevent the unnecessary suffering that can result when patients' dying preferences are unknown.

Impact of Repeated Reimbursement Penalties on Hospital Total Quality Scores.

OBJECTIVES: The incidence of hospital-acquired conditions (HACs) is a serious public health issue with implications ranging from patient morbidity and mortality to negative financial impacts on patients and health care systems. Despite substantial efforts to address and reduce HACs, research into the effect of quality improvement programs is inconclusive. This study seeks to better understand the relationship between repeated reimbursement penalties and improvement in HAC quality scores. METHODS: A quantitative comparative analysis of U.S. health care data was conducted. Data on quality outcomes and hospital characteristics were sourced from the Hospital-Acquired Condition Reduction Program from fiscal years 2018 and 2019 and the Centers for Medicare & Medicaid Services Inpatient Prospective Payment System impact files, respectively. RESULTS: In total, 3123 U.S. hospitals were analyzed to compare differences between total HAC scores of hospitals with and without penalties in consecutive years. Hospitals with repeated penalties had significantly greater improvement in scores ( t497.262 = -13.00, P < 0.001), and the impact was greatest in small hospitals (<100 beds). Repeated penalties had a smaller impact on disproportionate share hospitals (Cohen d = 0.73). Among all hospitals, the effect of repeated penalties was large (Cohen d = 0.75). CONCLUSIONS: This study suggests that repeated penalties can improve quality scores in U.S. hospitals. However, the effect may be exaggerated for smaller hospitals and those that serve patient populations with a relatively higher socioeconomic status. The reason disproportionate share hospitals did not show as much improvement as nondisproportionate hospitals may be because hospitals serving vulnerable populations often have fewer resources.

Supervised exercise training improves cardiorespiratory fitness and reduces perioperative risk in peripheral artery disease patients with intermittent claudication.

INTRODUCTION: This study examined to what extent supervised aerobic and resistance exercise combined with continued unsupervised exercise training improves cardiorespiratory fitness and corresponding perioperative risk in peripheral artery disease (PAD) patients with intermittent claudication. METHODS: A total of 106 patients (77% male) were enrolled into the study, alongside 155 healthy non-PAD control participants. Patients completed supervised exercise therapy (aerobic and resistance exercises of the upper and lower limbs) twice a week for 10 weeks. Thereafter, 52 patients completed 12 weeks of an unsupervised tailored home-based exercise. Pain-free walking distance (PWD), maximum walking distance (MWD), peak oxygen uptake ([Formula: see text]) and perioperative risk were assessed before and after both exercise interventions. RESULTS: Patients were highly unconditioned relative to healthy controls ([Formula: see text]=11.9 vs 24.2ml/kg/min, p=<0.001) with 91% classified as high perioperative risk (peak oxygen uptake <15ml/kg/min). Supervised exercise increased PWD (+44±81m, p=<0.001), MWD (+44±71m, p=<0.001) and [Formula: see text] (+1.01±1.63ml/kg/min, p=<0.001) and lowered perioperative risk (91% to 85%, p=<0.001). When compared with supervised exercise, the improvements in PWD were maintained following unsupervised exercise (+11±91m vs supervised exercise, p=0.572); however, MWD and [Formula: see text] decreased (-15±48m, p=0.030 and -0.34±1.11ml/kg/min, p=0.030, respectively) and perioperative risk increased (+3%, p=<0.001) although still below baseline (p=<0.001). CONCLUSIONS: Supervised aerobic and resistance exercise training and, to a lesser extent, unsupervised tailored exercise improves walking capacity and cardiorespiratory fitness and reduces perioperative risk in PAD patients with intermittent claudication.

Hospice Capacity to Provide General Inpatient Care: Emergency Department Utilization and Live Discharge Among Cancer Patients.

General inpatient (GIP) hospice care is used only minimally for hospice patients, and more than a quarter of Medicare hospice facilities do not provide GIP care. To determine the impact of hospices' capacity to provide on emergency department use during hospice enrollment and live discharge from hospice, we used Surveillance, Epidemiology, and End Results-Medicare linked data and CMS Provider of Services data from 2007 to 2013 from ten states and two metropolitan regions. Grouping hospices into three GIP care provision categories: 1) no-GIP; 2) GIP-contract; and 3) GIP-IHF where hospices directly provide GIP care in their own inpatient hospice facility (IHF), we built a multilevel logistic model that accounted for unobserved hospice characteristics. Nearly 9% of the study sample received GIP care, of which 82% received such care in the last week of discharge. GIP-IHF hospices had lower live discharge rates than no-GIP hospices (AOR: .61; 95% CI: .47-.79; P < .001) and GIP-contract hospices (AOR: .84; 95% CI: .70-1.00; P < .05). Similarly, GIP-contract hospices were also associated with a decreased risk of live discharge, compared to no-GIP hospices (AOR: .76; CI: .62-.92; P < .05). There was no difference in emergency department use between no-GIP hospices and hospices with such capacity. Our results suggest that hospices capable of providing GIP care have lower live discharge rates than their counterparts. However, the fact that GIP care tends to be provided too close to death limits its effectiveness in preventing avoidable emergency department use.

Measurement of Electron-Neutrino Charged-Current Cross Sections on

Using an 185-kg NaI[Tl] array, COHERENT has measured the inclusive electron-neutrino charged-current cross section on ^{127}I with pion decay-at-rest neutrinos produced by the Spallation Neutron Source at Oak Ridge National Laboratory. Iodine is one the heaviest targets for which low-energy (≤50 MeV) inelastic neutrino-nucleus processes have been measured, and this is the first measurement of its inclusive cross section. After a five-year detector exposure, COHERENT reports a flux-averaged cross section for electron neutrinos of 9.2_{-1.8}^{+2.1}×10^{-40} cm^{2}. This corresponds to a value that is ∼41% lower than predicted using the MARLEY event generator with a measured Gamow-Teller strength distribution. In addition, the observed visible spectrum from charged-current scattering on ^{127}I has been measured between 10 and 55 MeV, and the exclusive zero-neutron and one-or-more-neutron emission cross sections are measured to be 5.2_{-3.1}^{+3.4}×10^{-40} and 2.2_{-0.5}^{+0.4}×10^{-40} cm^{2}, respectively.

An online intervention to improve the health and well-being of informal caregivers of individuals with Alzheimer's disease: A pilot study.

Objective: Describe an intervention to improve the health and well-being of informal caregivers of individuals with Alzheimer's disease (AD) and present pilot program findings. Methods: Participants (N = 31, mean age = 45.7) were randomly assigned to one of two conditions: an online synchronous didactic lesson and peer support session series or an asynchronous didactic only session series. Outcome variables included physical health, nutrition intake, and stress. One-way ANOVA was conducted to examine the effects of the intervention. The least significant difference (LSD) post hoc test was used to analyze the difference pattern between means. Results: Participants in both conditions reported healthier dietary behavior and lower level of stress from pre-intervention to the post-intervention. These effects were not maintained at one-month follow up. Conclusion: An online educational intervention may improve the health and well-being of informal caregivers of people with AD. Further research is necessary to determine which specific intervention components to include and what strategies may help participants maintain improved health behaviors. Innovation: This program focused on the health and well-being of informal caregivers of individuals with AD rather than on emphasizing how caregivers can perform their caregiving duties better. The intervention was provided in an underserved lower-income, rural area.

Dynamic Patterns and Modeling of Early COVID-19 Transmission by Dynamic Mode Decomposition.

INTRODUCTION: Understanding the transmission patterns and dynamics of COVID-19 is critical to effective monitoring, intervention, and control for future pandemics. The aim of this study was to investigate the spatial and temporal characteristics of COVID-19 transmission during the early stage of the outbreak in the US, with the goal of informing future responses to similar outbreaks. METHODS: We used dynamic mode decomposition (DMD) and national data on COVID-19 cases (April 6, 2020-October 9, 2020) to model the spread of COVID-19 in the US as a dynamic system. DMD can decompose the complex evolution of disease cases into linear combinations of simple spatial patterns or structures (modes) with time-dependent mode amplitudes (coefficients). The modes reveal the hidden dynamic behaviors of the data. We identified geographic patterns of COVID-19 spread and quantified time-dependent changes in COVID-19 cases during the study period. RESULTS: The magnitude analysis from the dominant mode in DMD showed that California, Louisiana, Kansas, Georgia, and Texas had higher numbers of COVID-19 cases than other areas during the study period. States such as Arizona, Florida, Georgia, Massachusetts, New York, and Texas showed simultaneous increases in the number of COVID-19 cases, consistent with data from the Centers for Disease Control and Prevention. CONCLUSION: Results from DMD analysis indicate that certain areas in the US shared similar trends and similar spatiotemporal transmission patterns of COVID-19. These results provide valuable insights into the spread of COVID-19 and can inform policy makers and public health authorities in designing and implementing mitigation interventions.

A New Molecular Phylogeny of Salps (Tunicata: Thalicea: Salpida) and the Evolutionary History of Their Colonial Architecture.

Salps are marine pelagic tunicates with a complex life cycle, including a solitary and colonial stage composed of asexually budded individuals. These colonies develop into species-specific architectures with distinct zooid orientations, including transversal, oblique, linear, helical, and bipinnate chains, as well as whorls and clusters. The evolutionary history of salp colony architecture has remained obscured due to the lack of an ontology to characterize architectures, as well as a lack of phylogenetic taxon sampling and resolution of critical nodes. We (1) collected and sequenced eight species of salps that had never been sequenced before, (2) inferred the phylogenetic relationships among salps, and (3) reconstructed the evolutionary history of salp colony architecture. We collected salp specimens via offshore SCUBA diving, dissected tissue samples, extracted their DNA, amplified their 18S gene, and sequenced them using Sanger technology. We inferred the phylogeny of Salpida based on 18S using both Maximum Likelihood and Bayesian approaches. Using this phylogeny, we reconstructed the ancestral states of colony architecture using a Bayesian ordered Markov model informed by the presence and absence of specific developmental mechanisms that lead to each architecture. We find that the ancestral salp architecture is either oblique or linear, with every other state being derived. Moreover, linear chains have evolved independently at least three times. While transversal chains are developmentally basal and hypothesized to be ancestral, our phylogenetic topology and reconstructions strongly indicate that they are evolutionarily derived through the loss of zooid torsion. These traits are likely critical to multijet locomotory performance and evolving under natural selection. Our work showcases the need to study the broader diversity of salp species to gain a comprehensive understanding of their organismal biology, evolutionary history, and ecological roles in pelagic ecosystems.

Spanish Abstract Las salpas son tunicados pelágicos marinos con un ciclo vital complejo que incluye una fase solitaria y una colonial, compuesta de individuos gemados asexualmente. Al desarrollarse, estas colonias forman arquitecturas diferentes según la especie con orientaciones distintivas de los zooides. Estas arquitecturas incluyen las cadenas transversales, las oblícuas, las lineales, las solenoides, y también las formas de rueda y conglómero. La historia evolutiva de la arquitectura colonial de las salpas ha permanecido en la sombras debido a la falta de un ontología para caracterizar estas arquitecturas, además de por falta de representación taxonómica y resolución de nodos críticos en la filogenia. Hemos (1) muestreado y secuenciado ocho especies de salpa que nunca antes habían sido secuenciadas, (2) hemos inferido las relaciones filogenéticas entre salpas, y (3) reconstruido la historia evolutiva de la arquitectura colonial en salpas. Hemos obtenido especímenes de salpas mediante buceo con escafandra en alta mar, diseccionado muestras de tejido, extraído el ADN, amplificado y secuenciado el gen ribosomal 18S mediante tecnología Sanger. Hemos inferido la filogenia del orden Salpida en base al gen 18S utilizando tanto Máxima Verosimilitud como métodos Bayesianos. Utilizando esta filogenia, hemos reconstruido los estados ancestrales de la arquitectura colonial mediante un modelo Bayesiano Markov ordinal informado por la presencia y ausencia de mecanismos ontogenéticos que derivan en cada arquitectura. Hallamos que la arquitectura ancestral en las salpas fue o bien oblícua o lineal, con todos los demás estados derivados. Además, las cadenas lineales han evolucionado de forma independiente por lo menos tres veces. Las cadenas transversales son el estado basal en el desarrollo y han sido hipotetizadas como el estado ancestral. Sin embargo, nuestra topología filogenética y reconstrucciones indican firmemente que son en realidad derivadas a través de la pérdida del mecanismo de torsion de los zooides. Es probable que estos rasgos morfológicos sean críticos para la eficiencia locomotora de la propulsión multi-chorro y por tanto hayan evolucionado bajo el efecto de la selección natural. Nuestro trabajo demuestra la necesidad de estudiar la amplia diversidad de especies en las salpas para obtener una comprensión integral de su biología organísmica, historia evolutiva, y roles ecológicos en los ecosistemas pelágicos.

The effectiveness of community-based palliative care programme components: a systematic review.

BACKGROUND: There is evidence that community-based palliative care programmes can improve patient outcomes and caregiver experiences cost-effectively. However, little is known about which specific components within these programmes contribute to improving the outcomes. AIM: To systematically review research that evaluates the effectiveness of community-based palliative care components. DESIGN: A systematic mixed studies review synthesising quantitative, qualitative and mixed-methods study findings using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PROSPERO: ID # CRD42022302305. DATA SOURCES: Four databases were searched in August 2021 (CINAHL, Web of Science, ProQuest Federated and PubMed including MEDLINE) and a close review of included article references. Inclusion criteria required articles to evaluate a single, specific component of a community-based palliative care programme either within an individual programme or across several programmes. RESULTS: Overall, a total of 1,674 articles were identified, with 57 meeting the inclusion criteria. Of the included studies, 21 were qualitative, 25 were quantitative and 11 had mixed methods. Outcome measures consistently examined included patient/caregiver satisfaction, hospital utilisation and home deaths. The components of standardised sessions (interdisciplinary meetings about patients), volunteer engagement and early intervention contributed to the success of community-based palliative care programmes. CONCLUSIONS: Certain components of community-based palliative care programmes are effective. Such components should be implemented and tested more in low- and middle-income countries and key and vulnerable populations such as lower-income and marginalised racial or ethnic groups. In addition, more research is needed on the cost-effectiveness of individual programme components.

Health Behaviors, Financial Difficulties, and Depressive Symptoms Among Older Adults Across Gender and Race During the COVID-19 Pandemic.

Background: COVID-19 deeply affected the health and well-being of older adults. This study examines health behavior change and the interrelationships between health behaviors, financial difficulties, and depressive symptoms among older adults across gender and race during the pandemic. Methods: Using Rounds 1, 5, and 10 of the National Health and Aging Trends Study (NHATS) linked with the NHATS COVID-19 dataset, our sample included Medicare beneficiaries aged 65 or older in the U.S. (N = 3,118). We modeled the interrelationships between health behaviors, financial difficulties, and depressive symptoms using a structural equation model. Results: Female participants reported less walking, more changes in eating habits, less sleeping, and less alcohol consumption during the pandemic than before the pandemic compared to male participants. Compared to White, Non-White participants showed higher proportions of experiencing financial difficulties, less walking, less vigorous activity, and changes in time spent eating and sleeping during than before the pandemic. Financial difficulties was positively associated with depressive symptoms and sedentary behavior. Active behavior was negatively associated with depressive symptoms, while sedentary behavior was positively associated with more depressive symptoms. Discussion: Health professionals should consider health behaviors and financial difficulties when intervening on depressive symptoms experienced by older adults since the pandemic.

Performance metrics for models designed to predict treatment effect.

BACKGROUND: Measuring the performance of models that predict individualized treatment effect is challenging because the outcomes of two alternative treatments are inherently unobservable in one patient. The C-for-benefit was proposed to measure discriminative ability. However, measures of calibration and overall performance are still lacking. We aimed to propose metrics of calibration and overall performance for models predicting treatment effect in randomized clinical trials (RCTs). METHODS: Similar to the previously proposed C-for-benefit, we defined observed pairwise treatment effect as the difference between outcomes in pairs of matched patients with different treatment assignment. We match each untreated patient with the nearest treated patient based on the Mahalanobis distance between patient characteristics. Then, we define the Eavg-for-benefit, E50-for-benefit, and E90-for-benefit as the average, median, and 90th quantile of the absolute distance between the predicted pairwise treatment effects and local-regression-smoothed observed pairwise treatment effects. Furthermore, we define the cross-entropy-for-benefit and Brier-for-benefit as the logarithmic and average squared distance between predicted and observed pairwise treatment effects. In a simulation study, the metric values of deliberately "perturbed models" were compared to those of the data-generating model, i.e., "optimal model". To illustrate these performance metrics, different modeling approaches for predicting treatment effect are applied to the data of the Diabetes Prevention Program: 1) a risk modelling approach with restricted cubic splines; 2) an effect modelling approach including penalized treatment interactions; and 3) the causal forest. RESULTS: As desired, performance metric values of "perturbed models" were consistently worse than those of the "optimal model" (Eavg-for-benefit ≥ 0.043 versus 0.002, E50-for-benefit ≥ 0.032 versus 0.001, E90-for-benefit ≥ 0.084 versus 0.004, cross-entropy-for-benefit ≥ 0.765 versus 0.750, Brier-for-benefit ≥ 0.220 versus 0.218). Calibration, discriminative ability, and overall performance of three different models were similar in the case study. The proposed metrics were implemented in a publicly available R-package "HTEPredictionMetrics". CONCLUSION: The proposed metrics are useful to assess the calibration and overall performance of models predicting treatment effect in RCTs.

Emergence of Inducible Macrolide Resistance in Mycobacterium chelonae Due to Broad-Host-Range Plasmid and Chromosomal Variants of the Novel 23S rRNA Methylase Gene, erm(55).

Macrolides are a mainstay of therapy for infections due to nontuberculous mycobacteria (NTM). Among rapidly growing mycobacteria (RGM), inducible macrolide resistance is associated with four chromosomal 23S rRNA methylase (erm) genes. Beginning in 2018, we detected high-level inducible clarithromycin resistance (MICs of ≥16µg/mL) in clinical isolates of Mycobacterium chelonae, an RGM species not previously known to contain erm genes. Using whole-genome sequencing, we identified a novel plasmid-mediated erm gene. This gene, designated erm(55)P, exhibits <65% amino acid identity to previously described RGM erm genes. Two additional chromosomal erm(55) alleles, with sequence identities of 81% to 86% to erm(55)P, were also identified and designated erm(55)C and erm(55)T. The erm(55)T is part of a transposon. The erm(55)P allele variant is located on a putative 137-kb conjugative plasmid, pMchErm55. Evaluation of 133 consecutive isolates from 2020 to 2022 revealed 5 (3.8%) with erm(55). The erm(55)P gene was also identified in public data sets of two emerging pathogenic pigmented RGM species: Mycobacterium iranicum and Mycobacterium obuense, dating back to 2008. In both species, the gene appeared to be present on plasmids homologous to pMchErm55. Plasmid-mediated macrolide resistance, not described previously for any NTM species, appears to have spread to multiple RGM species. This has important implications for antimicrobial susceptibility guidelines and treatment of RGM infections. Further spread could present serious consequences for treatment of other macrolide-susceptible RGM. Additional studies are needed to determine the transmissibility of pMchErm55 and the distribution of erm(55) among other RGM species.