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Background: Uncomplicated urinary tract infection (UTI) is a common indication for outpatient antimicrobial therapy. National guidelines for the management of uncomplicated UTI were published by the Infectious Diseases Society of America in 2011, however it is not fully known the extent to which they align with current practices, patient diversity, and pathogen biology, all of which have evolved significantly in the time since their publication., Objective: We aimed to re-evaluate efficacy and adverse events for first-line antibiotics (nitrofurantoin, and trimethoprim-sulfamethoxazole), versus second-line antibiotics (fluoroquinolones) and versus alternative agents (oral β-lactams) for uncomplicated UTI in contemporary clinical practice by applying machine learning algorithms to a large claims database formatted into the Observational Medical Outcomes Partnership (OMOP) common data model., Outcomes: Our primary outcome was a composite endpoint for treatment failure, defined as outpatient or inpatient re-visit within 30 days for UTI, pyelonephritis or sepsis. Secondary outcomes were the risk of 4 common antibiotic-associated adverse events: gastrointestinal symptoms, rash, kidney injury and C. difficile infection., Statistical Methods: We adjusted for covariate-dependent censoring and treatment indication using a broad set of domain-expert derived features. Sensitivity analyses were conducted using OMOP-learn, an automated feature engineering package for OMOP datasets., Results: Our study included 57,585 episodes of UTI from 49,037 patients. First-line antibiotics were prescribed in 35,018 (61%) episodes, second-line antibiotics were prescribed in 21,140 (37%) episodes and alternative antibiotics were prescribed in 1,427 (2%) episodes. After adjustment, patients receiving first-line therapies had an absolute risk difference of -2.1% [95% CI -2.9% to -1.6%] for having a revisit for UTI within 30 days of diagnosis relative to second-line antibiotics. First-line therapies had an absolute risk difference of -6.6% [95% CI -9.4% to -3.8%] for 30-day revisit compared to alternative β-lactam antibiotics. Differences in adverse events were clinically similar between first and second line agents, but lower for first-line agents relative to alternative antibiotics (-3.5% [95% CI -5.9% to -1.2%]). Results were similar for models built with OMOPlearn., Conclusion: Our study provides support for the continued use of first-line antibiotics for the management of uncomplicated UTI. Our results also provide proof-of-principle that automated feature extraction methods for OMOP formatted data can emulate manually curated models, thereby promoting reproducibility and generalizability., Competing Interests: CONFLICTS OF INTEREST SDA reports support from Centers for Disease Control and Prevention SHEPheRD 75D30121D12733-D5-E003 (grant no. 5U54CK000616–02), the Society for Healthcare Epidemiology of America, and the Duke Claude D. Pepper Older Americans Independence Center (National Institute on Aging grant no. P30AG028716), as well as consulting fees from Locus Biosciences, Sysmex America, GlaxoSmithKline, bioMérieux, and the Infectious Diseases Society of America. SDA became an employee of GSK/ViiV Healthcare one year after her contribution to this project.

Background: Colorectal cancers (CRCs) from people with biallelic germline likely pathogenic/pathogenic variants in MUTYH or NTHL1 exhibit specific single base substitution (SBS) mutational signatures, namely combined SBS18 and SBS36 (SBS18+SBS36), and SBS30, respectively. The aim was to determine if adenomas from biallelic cases demonstrated these mutational signatures at diagnostic levels., Methods: Whole-exome sequencing of FFPE tissue and matched blood-derived DNA was performed on 9 adenomas and 15 CRCs from 13 biallelic MUTYH cases, on 7 adenomas and 2 CRCs from 5 biallelic NTHL1 cases and on 27 adenomas and 26 CRCs from 46 non-hereditary (sporadic) participants. All samples were assessed for COSMIC v3.2 SBS mutational signatures., Results: In biallelic MUTYH cases, SBS18+SBS36 signature proportions in adenomas (mean±standard deviation, 65.6%±29.6%) were not significantly different to those observed in CRCs (76.2%±20.5%, p-value =0.37), but were significantly higher compared with non-hereditary adenomas (7.6%±7.0%, p-value =3.4×10 -4 ). Similarly, in biallelic NTHL1 cases, SBS30 signature proportions in adenomas (74.5%±9.4%) were similar to those in CRCs (78.8%±2.4%) but significantly higher compared with non-hereditary adenomas (2.8%±3.6%, p-value =5.1×10 -7 ). Additionally, a compound heterozygote with the c.1187G>A p.(Gly396Asp) pathogenic variant and the c.533G>C p.(Gly178Ala) variant of unknown significance (VUS) in MUTYH demonstrated high levels of SBS18+SBS36 in four adenomas and one CRC, providing evidence for reclassification of the VUS to pathogenic., Conclusions: SBS18+SBS36 and SBS30 were enriched in adenomas at comparable proportions observed in CRCs from biallelic MUTYH and biallelic NTHL1 cases, respectively. Therefore, testing adenomas may improve the identification of biallelic cases and facilitate variant classification, ultimately enabling opportunities for CRC prevention., Competing Interests: Robert C. Grant received a scholarship from Pfizer and provided consulting or advisory roles for Astrazeneca, Tempus, Eisai, Incyte, Knight Therapeutics, Guardant Health, and Ipsen. All other authors have no relevant financial or non-financial interests to disclose.

Breathwork is an understudied school of practices involving intentional respiratory modulation to induce an altered state of consciousness (ASC). We simultaneously investigate the phenomenological and neural dynamics of breathwork by combining Temporal Experience Tracing, a quantitative methodology that preserves the temporal dynamics of subjective experience, with low-density portable EEG devices. Fourteen novice participants completed a course of up to 28 breathwork sessions-of 20, 40, or 60 min-in 28 days, yielding a neurophenomenological dataset of 301 breathwork sessions. Using hypothesis-driven and data-driven approaches, we found that "psychedelic-like" subjective experiences were associated with increased neural Lempel-Ziv complexity during breathwork. Exploratory analyses showed that the aperiodic exponent of the power spectral density-but not oscillatory alpha power-yielded similar neurophenomenological associations. Non-linear neural features, like complexity and the aperiodic exponent, neurally map both a multidimensional data-driven composite of positive experiences, and hypothesis-driven aspects of psychedelic-like experience states such as high bliss., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The contents of awareness can substantially change without any modification to the external world. Such effects are exemplified in binocular rivalry, where a different stimulus is presented to each eye causing instability in perception. This phenomenon has made binocular rivalry a quintessential method for studying consciousness and the necessary neural correlates for awareness. However, to conduct research on binocular rivalry usually requires self-reports of changes in percept, which can produce confounds and exclude states and contexts where self-reports are undesirable or unreliable. Here, we use a novel multivariate spatial filter dubbed 'Rhythmic Entrainment Source Separation' to extract steady state visual evoked potentials from electroencephalography data. We show that this method can be used to quantify the perceptual switch-rate of participants during binocular rivalry and therefore may be valuable in experimental contexts where self-reports are methodologically problematic or impossible, particularly as an adjunct. Our analyses also reveal that 'no-report' conditions may affect the deployment of attention and thereby neural correlates, another important consideration for consciousness research., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA)., Design: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as "important" or "essential" by ≥80% of participants were retained, and participants could suggest additional domains. In Round 2, participants rated their level of agreement that each domain was essential for evaluating OAMPs: 0 = strongly disagree to 10 = strongly agree. A domain was retained if ≥80% rated it ≥6. In Round 3, participants rated remaining domains using same scale as in Round 2; a domain was recommended as "core" if ≥80% of participants rated it ≥9 and as "optional" if ≥80% rated it ≥7., Results: A total of 178 individuals from 26 countries participated; 85 completed all survey rounds. Only one domain, "ability to participate in daily activities", met criteria for a core domain; 25 domains met criteria for an optional recommendation: 8 Patient Impacts, 5 Implementation Outcomes, 5 Participant Characteristics, 3 OAMP Characteristics and 4 Clinician Characteristics., Conclusion: The ability of patients with OA to participate in daily activities should be evaluated in all OAMPs. Teams evaluating OAMPs should consider including domains from the optional recommended set, with representation from all five categories and based on stakeholder priorities in their local context., (Published by Elsevier Ltd.)

Background: PALB2 is the most important contributor to familial breast cancer after BRCA1 and BRCA2 . Large genomic rearrangements (LGRs) in BRCA1 and BRCA2 are routinely assessed in clinical testing and are a significant contributor to the yield of actionable findings. In contrast, the contribution of LGRs in PALB2 has not been systematically studied., Methods: We performed targeted sequencing and real-time qPCR validation to identify LGRs in PALB2 in 5770 unrelated patients with familial breast cancer and 5741 cancer-free control women from the same Australian population., Results: Seven large deletions ranging in size from 0.96 kbp to 18.07 kbp involving PALB2 were identified in seven cases, while no LGRs were identified in any of the controls. Six LGRs were considered pathogenic as they included one or more exons of PALB2 and disrupted the WD40 domain at the C terminal end of the PALB2 protein while one LGR only involved a partial region of intron 10 and was considered a variant of unknown significance. Altogether, pathogenic LGRs identified in this study accounted for 10.3% (6 of 58) of the pathogenic PALB2 variants detected among the 5770 families with familial breast cancer., Conclusions: Our data show that a clinically important proportion of PALB2 pathogenic mutations in Australian patients with familial breast cancer are LGRs. Such observations have provided strong support for inclusion of PALB2 LGRs in routine clinical genetic testing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Cost and transportation are two commonly cited barriers to accessing health care in both human and veterinary medicine within underserved communities. While human medicine has utilized telehealth as a means of breaking down this barrier, limited research exists to describe its use in veterinary medicine. The Pets for Life (PFL) program has partnered with the Penn Vet Shelter Medicine Program to provide veterinary appointments to clients, at no cost to the client, in underserved zip codes through virtual telehealth visits. These visits incorporated veterinary students as part of their clinical rotations through a service learning based model. Between January and August 2021, 31 PFL clients and nine veterinary students completed surveys to describe the role of telehealth in addressing barriers to accessing veterinary care, their perceptions of telehealth appointments, the human-animal bond, and changes in veterinary student empathy. PFL clients completed the survey immediately following their telehealth appointment, and veterinary students completed surveys prior to and following their participation in the PFL appointments during the rotation. Nearly 25% of clients reported that they would not have been able to secure transportation and 58% reported they would not have been able to afford an appointment at an in-person veterinary clinic. The population of clients who responded that cost was a significant barrier to accessing care did not entirely overlap with those who responded that transportation was a significant barrier to accessing care, indicating support for the use of telehealth in providing an alternative modality to address transportation challenges as a barrier to accessing veterinary care. Additional data suggests that both client and student experience was overwhelmingly positive, providing support for further service learning initiatives in veterinary student education. Further research is warranted to continue to assess the emerging role of telehealth in improving veterinary care for underserved communities., Competing Interests: EH was employed by Philadelphia Animal Welfare Society. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lundahl, Powell, Reinhard, Healey and Watson.)

The philosophical underpinning of trials of complex interventions is critiqued for not taking into account causal mechanisms that influence potential outcomes. In this article, we draw from in-depth interviews (with practice nurses and patients) and observations of practice meetings and consultations to investigate the outcomes of a complex intervention to promote self-management (in particular exercise) for osteoarthritis in primary care settings. We argue that nurses interpreted the intervention as underpinned by the need to educate rather than work with patients, and, drawing from Habermasian theory, we argue that expert medicalised knowledge (system) clashed with lay 'lifeworld' prerogatives in an uneven communicative arena (the consultation). In turn, the advice and instructions given to patients were not always commensurate with their 'lifeworld'. Consequently, patients struggled to embed exercise routines into their daily lives for reasons of unsuitable locality, sense-making that 'home' was an inappropriate place to exercise and using embodied knowledge to test the efficacy of exercise on pain. We conclude by arguing that using Habermasian theory helped to understand reasons why the trial failed to increase exercise levels. Our findings suggest that communication styles influence the outcomes of self-management interventions, reinforce the utility of theoretically informed qualitative research embedded within trials to improve conduct and outcomes and indicate incorporating perspectives from human geography can enhance Habermas-informed research and theorising.

Background: This study assessed the measurement properties of two commonly used self-report physical activity (PA) measures: the International Physical Activity Questionnaire-Short Form (IPAQ-SF) and the Physical Activity Scale for the elderly (PASE) in adults with osteoarthritis., Methods: Secondary analysis of the MOSAICS cluster randomised controlled trial baseline and 3-month follow-up questionnaires, total scores and subdomains of the IPAQ-SF and PASE were compared. Intra-class correlations (ICC) were used to assess test-retest reliability, measurement error was assessed using standard error of measurement (SEM), smallest detectable change (SDC) and 95% limits of agreement (LoA). Responsiveness was assessed using effect size (ES), standard responsive measurement (SRM) and response ratio (RR)., Results: There was moderate correlation (r = 0.56) between the total IPAQ-SF scores (score ranges 0-16,398) and the total PASE scores (score ranges 0-400). Subdomain correlations were also moderate (ranges 0.39-0.57). The PASE showed greater reliability compared to the IPAQ-SF (ICC = 0.68; 0.61-0.74 95% CI and ICC = 0.64; 0.55-0.72, respectively). Measurement errors in both measures were large: PASE SEM = 46.7, SDC = 129.6 and 95% LoA ranges = -117 to 136, the IPAQ-SF SEM = 3532.2 METS -1 min-1 week , SDC = 9790.8 and 95% LoA ranges = -5222 to 5597. Responsiveness was poor: ES -0.14 and -0.16, SRM -0.21 and -0.21, and RR 0.12 and 0.09 for the IPAQ-SF and PASE, respectively., Discussion: The IPAQ-SF and PASE appear limited in reliability, measurement error and responsiveness. Researchers and clinicians should be aware of these limitations, particularly when comparing different levels of PA and monitoring PA levels changes over time in those with osteoarthritis., (© 2021 John Wiley & Sons Ltd.)

Suppression of established populations of invasive alien species can be a complex and expensive process, which is frequently unsuccessful. The Asian clam, Corbicula fluminea (Müller, 1774), is considered a high impact invader that can adversely alter freshwater ecosystems and decrease their socioeconomic value. To date, C. fluminea continues to spread and persist within freshwater environments worldwide, despite repeated management attempts to prevent dispersal and suppress established populations. As extensive C. fluminea beds can often become exposed during low-water conditions, the direct application of hot or cold thermal shock treatments has been proposed as suitable mechanism for their control. Further, mechanical substrate disturbance may enhance the efficacy of thermal shock treatments by facilitating exposures to multiple layers of buried clams. In the present study, we advanced these methods by assessing combined applications of both hot and cold thermal shock treatments for control of C. fluminea, using steam spray (≥100 °C; 350 kPa), low- or high-intensity open-flame burns (~1000 °C) and dry ice (-78 °C). In a direct comparison of raking combined with hot thermal shock applications, both steam and high-intensity open-flame treatments tended to be most effective, especially following multiple applications. In addition, when hot thermal treatments are followed by a final cold shock (i.e. dry ice), steam treatments tended to be most effective. Further, when dry ice was applied either alone or prior to an application of a hot shock treatment, substantial if not complete C. fluminea mortality was observed. Overall, this study demonstrated that combined applications of hot and cold thermal shock treatments, applied following the disruption of the substrate, can substantially increase C. fluminea mortality compared to separate hot or cold treatments.

Objective: 1) To identify potential moderators of the effect of therapeutic exercise explored in randomised controlled trials (RCTs) of knee and hip osteoarthritis (OA); 2) summarise the extent, strength and quality of evidence reported for moderators., Design: Systematic review (PROSPERO CRD42019148074). Inclusion criteria: a) RCTs with sub-group analyses investigating potential moderator variables; b) participants with knee and/or hip OA; c) therapeutic exercise interventions compared to either no exercise control or alternative exercise intervention(s), and; d) measuring pain or physical function outcomes. Included RCTs' risk of bias and sub-group analysis quality were assessed. Data were extracted on sub-group analyses (methods and potential moderators), outcomes (pain and function) and sub-group findings (associated statistics of potential moderator∗intervention effects). Findings were analysed using narrative synthesis., Results: 14 RCTs were included; 13 knee OA RCTs (n = 2743 participants) explored 23 potential moderators and 1 hip OA RCT (n = 203) explored 6 potential moderators. Sub-group analysis quality was mixed. Knee varus malalignment was the only moderator of therapeutic exercise compared to non-exercise control in 1 RCT (WOMAC-pain adjusted difference 12.7 in the neutral alignment sub-group and 1.8 in the malaligned sub-group, interaction term: p = 0.02). Varus thrust, knee laxity/instability, obesity and cardiac problems all moderated the effect of therapeutic exercise on pain or function compared to different comparison exercise., Conclusions: Therapeutic exercise may be effective for reducing pain in people with knee OA and neutral alignment but not for those with varus malalignment. The exercise moderator literature is limited. More robust evidence is required to inform sub-group exercise selection., Competing Interests: There is no conflict of interest for any of the authors., (© 2020 The Authors.)

While artificial pancreas (AP) systems are expected to improve the quality of life among people with type 1 diabetes mellitus (T1DM), the design of convenient systems that optimize the user experience, especially for those with active lifestyles, such as children and adolescents, still remains an open research question. In this work, we introduce an embeddable design and implementation of model predictive control (MPC) of AP systems for people with T1DM that significantly reduces the weight and on-body footprint of the AP system. The embeddable controller is based on a zone MPC that has been evaluated in multiple clinical studies. The proposed embedded zone MPC features a simpler design of the periodic safe zone in the cost function and the utilization of state-of-the-art alternating minimization algorithms for solving the convex programming problems inherent to MPC with linear models subject to convex constraints. Off-line closed-loop data generated by the FDA-accepted UVA/Padova simulator is used to select an optimization algorithm and corresponding tuning parameters. Through hardware-in-the-loop in silico results on a limited-resource Arduino Zero (Feather M0) platform, we demonstrate the potential of the proposed embedded MPC. In spite of resource limitations, our embedded zone MPC manages to achieve comparable performance of that of the full-version zone MPC implemented in a 64-bit desktop for scenarios with/without meal-disturbance compensations. Metrics for performance comparison included median percent time in the euglycemic ([70, 180] mg/dL range) of 84.3% vs. 83.1% for announced meals, with an equivalence test yielding p = 0.0013 and 66.2% vs. 66.0% for unannounced meals with p = 0.0028.

Background: Despite considerable encouragement for healthcare professionals to use or be clear about the theory used in their improvement programmes, the uptake of these approaches to design interventions or report their content is lacking. Recommendations suggest healthcare practitioners work with social and/or behavioural scientists to gain expertise in programme theory, ideally before, but even during or after the work is done. We aim to demonstrate the extent to which intuitive intervention strategies designed by healthcare professionals to overcome patient barriers to communicating genetic cancer risk information to family members align with a theoretical framework of behaviour change., Methods: As part of a pre-post intervention study, a team of genetic counsellors aimed to understand, and design interventions to overcome, the major barriers a group of familial cancer patients face around communicating hereditary cancer risk information to their relatives. A behavioural change specialist worked with the team to review and recode barriers and interventions according to the Theoretical Domains Framework (TDF) and 93 behaviour change techniques (BCTs). Resulting BCTs were cross-referenced against the Theory and Techniques Tool to examine whether evidence-based mechanistic links have been established to date., Results: Five themes emerged from the genetic counsellor coded barriers, which when recoded according to the TDF represented seven domains of behaviour change. Forty-five experiential and intuitive interventions were used to tackle key barriers. These were represented by 21 BCTs, which were found to be used on 131 occasions. The full mapping exercise is presented, resulting in a suite of intervention strategies explicitly linked to a theoretical framework. Structured, written reflections were provided retrospectively by the core clinical team., Conclusions: Although the ideal is to use theory prospectively, or even whilst a project is underway, making links between theory and interventions explicit, even retrospectively, can contribute towards standardising intervention strategies, furthering understanding of intervention effects, and enhancing the opportunities for accurate replicability and generalisability across other settings. Demonstrating to healthcare professionals how their intuition aligns with theory may highlight the additional benefits that theory has to offer and serve to promote its use in improvement., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Control strategies for established populations of invasive alien species can be costly and complex endeavours, which are frequently unsuccessful. Therefore, rapid-reaction techniques that are capable of maximising efficacy whilst minimising environmental damage are urgently required. The Asian clam (Corbicula fluminea Müller, 1774), and the zebra mussel (Dreissena polymorpha Pallas, 1771), are invaders capable of adversely affecting the functioning and biodiversity of freshwater ecosystems. Despite efforts to implement substantial population-control measures, both species continue to spread and persist within freshwater environments. As bivalve beds often become exposed during low-water conditions, this study examined the efficacy of steam-spray (≥100 °C, 350 kPa) and open-flame burn treatments (~1000 °C) to kill exposed individuals. Direct steam exposure lasting for 5 min caused 100% mortality of C. fluminea buried at a depth of 3 cm. Further, combined rake and thermal shock treatments, whereby the substrate is disturbed between each application of either a steam or open flame, caused 100% mortality of C. fluminea specimens residing within a 4-cm deep substrate patch, following three consecutive treatment applications. However, deeper 8-cm patches and water-saturated substrate reduced maximum bivalve species mortality rates to 77% and 70%, respectively. Finally, 100% of D. polymorpha specimens were killed following exposure to steam and open-flame treatments lasting for 30 s and 5 s, respectively. Overall, our results confirm the efficacy of thermal shock treatments as a potential tool for substantial control of low-water-exposed bivalves. Although promising, our results require validation through upscaling to field application, with consideration of other substrate types, increased substrate depth, greater bivalve densities, non-target and long-term treatment effects.