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Background: Accessible contraception is critical for promoting the health and well-being of women and their families. In the UK, contraception is free at the point of access, but only 55% of pregnancies are planned, with negative implications for maternal and infant outcomes. In general, women from ethnic minorities use contraceptives less than white women. Barriers to the uptake of contraceptives have been identified, including perceived poor information from healthcare professionals and concerns about side effects. However, most studies do not include representative proportions of women from ethnic minorities. Evidence suggests that ethnic minority (EM) women feel targeted and coerced by healthcare professionals regarding contraception., Methods: A systematic search of Medline, Embase, and PsycINFO via Ovid, CINAHL, and Web of Science was conducted to identify primary qualitative and mixed-methods studies exploring ethnic minority women's experience of contraception in the UK. The data were charted using thematic analysis, using both summary and synthesis., Results and Conclusions: 16 studies met the inclusion criteria, including the perspectives of 717 participants from an ethnic minority. Four overarching themes were developed: contraceptive knowledge, beliefs, family, and services. Similar to women in general, ethnic minority women have concerns about side effects, especially infertility, value the perspectives of their peers and male partners, and express a preference for female healthcare professionals. Novel perspectives included conflicting ideas about the influence of religion and stereotyping of ethnic minority women. Culturally competent consultations and a better understanding of hormonal hesitancy are essential., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The iRefer guidelines provide evidence-based recommendations on imaging and are designed to facilitate appropriate referrals and limit unnecessary radiation exposure. In 2017, a review at this institution assessed the appropriateness of imaging referrals. This study provides an update 5 years later on the referral appropriateness and aims to assess what impact the previous review has had on referral appropriateness., Methods: A retrospective study of 945 referrals across GPs, ED, and inpatients was audited against the iRefer guidelines with costs and cumulative dose estimates calculated for inappropriate referrals considering salaries of those involved, the average time spent performing and reporting radiographs, and the median effective dose values., Results: Results show a decrease in the volume of requests overall with the relative proportion of inappropriate requests rising significantly. Inappropriate requests for abdominal X-rays from GPs decreased from 72 to 37.5%, whereas inappropriate ED referrals increased from 38 to 46% and inappropriate inpatient requests remained static at 30%. The proportion of inappropriate GP requests for spinal radiographs significantly increased for cervical, thoracic, and lumbar spine radiographs, respectively (18 to 66%; 47 to 72%; 53 to 80%; p-value < 0.001). Inappropriate radiographs represent an increased financial and dose-based burden., Conclusion: The volume of radiograph requests reduced after over a 5-year interval; however, the relative proportion of inappropriate requests rose significantly. The iRefer guidelines provide a useful resource to ensure that imaging is used appropriately, effectively, and safely; however, more work is needed to ensure that requests are adhering to these guidelines., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Brief interventions for smoking cessation, such as the 5As (ask, assess, advise, assist, arrange) are effective, but limited data are available regarding their delivery to smokers with mental health disorders (MHDs), and whether a disparity in care exists. This study explored the difference in the self-reported receipt of 5As between smokers with and without MHDs in a community setting. Baseline data from 1452 (1206 without and 246 with self-reported MHDs) Australian smokers who participated in a smoking cessation trial were analysed. Participants reported interactions with healthcare providers and receipt of the 5As over the past 12 months. Multivariate logistic regression analysis was employed to investigate the association between receipt of the 5As and MHD status. Smokers with MHDs were significantly more likely to be asked, assessed, advised, and assisted compared to those without MHDs, but arranging follow-up was very low in both groups (7.7% with MHDs and 4.1% without MHDs). This is particularly concerning for vulnerable population like smokers with MHDs, who may struggle more in their quit attempt. The findings highlight the need to enhance the implementation of the 'arrange follow-up' component to improve cessation outcomes and reduce health disparities., Competing Interests: Declaration of competing interest Declaration of interests: none., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Despite significant changes in healthcare, work practices, and leisure activity, the proposed precipitating factors for abdominal wall hernias have remained largely unchanged for almost two centuries. We aimed to investigate if there have been shifts in these factors over time by examining patients' perception of precipitating factors for abdominal wall hernia development. This study was conducted in the Royal College of Surgeons In Ireland Department of Surgery, Connolly Hospital, Blanchardstown, Dublin, where patients with abdominal wall hernias completed a questionnaire  ., Results: A total of 277 patients (mean age 55.7; 85.6% male) with abdominal wall hernia completed the questionnaire (66.1% inguinal; 10.8% umbilical; 6.9% paraumbilical; 10.5% epigastric; 3.2% incisional; 1.4% femoral, and 1.1% port-site). One hundred and twenty patients (43.3%) believed their hernia was due to lifting, 71 (25.6%) cited gym activity and 17 (6.1%) cited other sporting activities as the precipitating factor. Traditional factors - chronic cough and constipation - were cumulatively cited only by 11 patients (4.0%), while prostatic obstruction was not cited by any., Conclusion: This study suggests that fitness pursuits may be an increasing contributor to the development of abdominal wall hernia. Greater attention should be paid to the proper use of gym equipment to minimise the risk of hernia development., (© 2024. The Author(s).)

Objectives: To assess the potential number of European Union (EU) population(s), intervention, comparator(s), and outcomes (PICOs) based on European Network for Health Technology Assessment 21 (EUnetHTA 21) guidance and to explore further evidence-based opportunities to produce more predictable and workable EU PICOs., Methods: The consolidated EU PICOs of 2 future hypothetical medicines in first-line non-small cell lung cancer (1L NSCLC) and third line multiple myeloma (3L MM) were derived using published health technology assessment reports of 2 recent medicines in similar indications based on EUnetHTA 21 proposed guidance. Sensitivity analysis assessed the impact of additional PICO requests. The number of analyses requested was estimated., Results: In 1L NSCLC and 3L MM, 6 and 9 EU Member States (MS), respectively, had published health technology assessment reports. PICO consolidation resulted in 10 PICOs for 1L NSCLC and 16 PICOs for 3L MM, increasing to 14 and 18 PICOs, respectively, when England's National Institute for Health and Care Excellence scope was included to proxy remaining MS. A minimum of 280 and 720 analyses would be requested, exponentially increasing as additional outcome measures and subgroups are requested., Conclusions: The PICO approach outlined by EUnetHTA 21 results in a significant number of analysis requests and substantial resources. Use of complementary analyses alongside evidence-based methods to derive PICOs and engaging with the health technology developer throughout the process would create a workable EU PICO that is predictable and most impactful for the EU, resulting in a timely and high-quality assessment report that is more usable at a MS level., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

In the European Medicines Agency (EMA) "Guideline for Environmental Risk Assessment of Medicinal Products for Human Use," a fish bioconcentration factor (BCF) study is triggered in Phase I for pharmaceuticals having log Kow >4.5, to support Persistence, Bioaccumulation and Toxicity (PBT) screening, and in Phase II to assess secondary poisoning and bioaccumulation ('B') potential when log Kow ≥3. The standard sampling schedule outlined in OECD Test Guideline 305 (TG305) may require assessment of approximately 200 fish following exposure to low- and high-test concentrations and a negative control. We report experimental log Kow and BCF values for 64 human pharmaceuticals that were used to evaluate the current BCF testing trigger of log Kow ≥3, and whether a single BCF exposure concentration allows accurate classification of bioaccumulation potential. Our data support raising the BCF testing trigger to log Kow ≥4, and use of a single test concentration. The resulting reduction in the use of fish is consistent with the 3 R s principle and did not adversely affect classification accuracy. An assessment of potential risk of secondary poisoning was also conducted for three drugs classified as either B or vB, and no risks were identified., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Second-generation direct-acting antivirals (2G DAA) to cure HCV have led to dramatic clinical improvements. HCV-associated hepatocellular carcinoma (HCC), however, remains common. Impaired immune tumor surveillance may play a role in HCC development. Our cohort evaluated the effects of innate immune types and clinical variables on outcomes including HCC., Methods: Participants underwent full HLA class I/KIR typing and long-term HCV follow-up., Results: A total of 353 HCV+ participants were followed for a mean of 7 years. Cirrhosis: 25% at baseline, developed in 12% during follow-up. 158 participants received 2G DAA therapy. HCC developed without HCV therapy in 20 subjects, 24 HCC after HCV therapy, and 10 of these after 2G DAA. Two predictors of HCC among 2G DAA-treated patients: cirrhosis (OR, 10.0, p = 0.002) and HLA/KIR profiles predicting weak natural killer (NK) cell-mediated immunity (NK cell complementation groups 6, 9, 11, 12, OR of 5.1, p = 0.02). Without 2G DAA therapy: cirrhosis was the main clinical predictor of HCC (OR, 30.8, p < 0.0001), and weak NK-cell-mediated immunity did not predict HCC., Conclusion: Cirrhosis is the main risk state predisposing to HCC, but weak NK-cell-mediated immunity may predispose to post-2G DAA HCC more than intermediate or strong NK-cell-mediated immunity., (© ([0‐9]+) Wiley‐VCH GmbH.)

Background: Large Vessel Occlusion (LVO) screening tools provide objective assessments to guide diagnostic decisions during acute stroke activations. The Stroke VAN screening tool includes weakness, vision, aphasia, and neglect; however, only screens positive if weakness is present regardless of presence of other symptoms including isolated aphasia. The purpose of this project was to evaluate wAve, a modified Stroke VAN screening tool. WAve includes components of VAN with emphasis on isolated aphasia., Methods: We conducted a retrospective cohort study on 376 persons who presented with stroke symptoms within 24 h of last known well (LKW) to the Emergency Department of an urban comprehensive stroke center in north central Texas between July 2019 and January 2020. Comparison of VAN and wAve predictive values was calculated using Chi square analysis. Sensitivity and specificity was checked by using MedCalc software. Data from the electronic medical record was obtained for analysis including a documented wAve score and a calculated VAN score. Results of CT angiogram diagnostic testing was used to determine congruence of screening results with evidence of LVO. Power analysis described by Hajian- Tilaki was used to estimate study size., Results: Results included 192 positive wAve screens and 184 negative wAve screens compared to 152 positive VAN screens and 224 negative VAN screens. The sensitivities for wAve and VAN were 89 % and 80 % respectively. Negative predictive values for wAve and VAN were 97 % and 95 % respectively. In isolated aphasic person, one of eight presented with a LVO and received intervention., Conclusion: The team discovered more LVOs were identified with wAve than VAN in persons exhibiting isolated aphasia symptoms. Larger studies are needed to understand the role isolated aphasia plays in LVO detection., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Real-time prediction of histologic features of small colorectal polyps may prevent resection and/or pathologic evaluation and therefore decrease colonoscopy costs. Previous studies showed that computer-aided diagnosis (CADx) was highly accurate, though it did not outperform expert endoscopists., Objective: To assess the diagnostic performance of histologic predictions by general endoscopists before and after assistance from CADx in a real-life setting., Design: Prospective, multicenter, single-group study. (ClinicalTrials.gov: NCT04437615)., Setting: 6 centers across the United States., Participants: 1252 consecutive patients undergoing colonoscopy and 49 general endoscopists with variable experience in real-time prediction of polyp histologic features., Intervention: Real-time use of CADx during routine colonoscopy., Measurements: The primary end points were the sensitivity and specificity of CADx-unassisted and CADx-assisted histologic predictions for adenomas measuring 5 mm or less. For clinical purposes, additional estimates according to location and confidence level were provided., Results: The CADx device made a diagnosis for 2695 polyps measuring 5 mm or less (96%) in 1252 patients. There was no difference in sensitivity between the unassisted and assisted groups (90.7% vs. 90.8%; P = 0.52). Specificity was higher in the CADx-assisted group (59.5% vs. 64.7%; P < 0.001). Among all 2695 polyps measuring 5 mm or less, 88.2% and 86.1% ( P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be resected and discarded without pathologic evaluation. Among 743 rectosigmoid polyps measuring 5 mm or less, 49.5% and 47.9% ( P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be left in situ without resection., Limitation: Decision making based on CADx might differ outside a clinical trial., Conclusion: CADx assistance did not result in increased sensitivity of optical diagnosis. Despite a slight increase, the specificity of CADx-assisted diagnosis remained suboptimal., Primary Funding Source: Olympus America Corporation served as the clinical study sponsor., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0086.

Purpose: Prostate biopsy is central to the accurate histological diagnosis of prostate cancer. In current practice, the biopsy procedure can be performed using a transrectal or transperineal route with different technologies available for targeting of lesions within the prostate. Historically, the biopsy procedure was performed solely by urologists, but with the advent of image-guided techniques, the involvement of radiologists in prostate biopsy has become more common. Herein, we discuss the pros, cons and future considerations regarding their ongoing role., Methods: A narrative review regarding the current evidence was completed. PubMed and Cochrane central register of controlled trials were search until January 2024. All study types were of consideration if published after 2000 and an English language translation was available., Results: There are no published studies that directly compare outcomes of prostate biopsy when performed by a urologist or radiologist. In all published studies regarding the learning curve for prostate biopsy, the procedure was performed by urologists. These studies suggest that the learning curve for prostate biopsy is between 10 and 50 cases to reach proficiency in terms of prostate cancer detection and complications. It is recognised that many urologists are poorly able to accurately interpret multi parametric (mp)-MRI of the prostate. Collaboration between the specialities is of importance with urology offering the advantage of being involved in prior and future care of the patient while radiology has the advantage of being able to expertly interpret preprocedure MRI., Conclusion: There is no evidence to suggest that prostate biopsy should be solely performed by a specific specialty. The most important factor remains knowledge of the relevant anatomy and sufficient volume of cases to develop and maintain skills., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Stakeholder involvement has long been considered a success factor for a joint European health technology assessment (HTA) process, and its relevance is now anchored in the EU HTA Regulation's (EU HTAR) legislative wording. Therefore, we aimed to explore the roles, challenges, and most important activities to increase the level of involvement per stakeholder group., Methods: At the 2022 Fall Convention of the European Access Academy (EAA), working groups addressed the involvement of patients, clinicians, regulators, health technology developers (HTD), and national HTA bodies and payers within the EU HTA process. Each working group revisited the pre-convention survey results, determined key role characteristics for each stakeholder, and agreed on the most important activities to fulfill the role profile. Finally, the activities suggested per group were prioritized by plenary group., Results: The prioritized actions for patients included training and capacity building, the establishment of a patient involvement committee, and the establishment of a patient unit at the EC secretariat. For clinicians, it included alignment on evidence assessment from a clinical vs. HTA point of view, capacity building, and standardization of processes. The most important actions for regulators are to develop joint regulatory-HTA guidance documents, align processes and interfaces under the regulation, and share discussions on post-licensing evidence generation. HTDs prioritized scientific advice capacity and the review of the scoping process, and further development of the scope of the assessment report fact checks. The top three actions for national HTA bodies and payers included clarification on the early HTD dialogue process, political support and commitment, and clarification on financial support., Conclusions: Addressing the activities identified as the most important for stakeholders/collaborators in the EU HTA process (e.g., in the implementation of the EU HTA Stakeholder Network and of the guidance documents developed by the EUnetHTA 21 consortium) will be key to starting an " inclusive civil society dialogue ", as suggested by the European Commission's Pharmaceutical Strategy., Competing Interests: Conflicts of InterestT.D.: no CoI; W.V.D.: no CoI; S.S.: no CoI; I.H.: no CoI; R.G.: no CoI; M.T.: no CoI; C.D.: as a strategic and legal consultant, regularly receives honoraria for consulting from numerous health technology developers; J.D.: as a strategic and legal consultant, regularly receives honoraria for consulting from numerous health technology developers; A.C.: no CoI; F.H.: no CoI; M.P.: no CoI; M.B.: no CoI; P.M.: no CoI; A.S.: no CoI; W.G.: no CoI; F.G.: no CoI; S.C.: no CoI; J.R. (James Ryan): employed by AstraZeneca; P.D.: employed by Abbvie; O.S.-M.: no CoI., (© 2024 by the authors.)

Habitat fragmentation can increase the chance of population bottlenecks and inbreeding, and may ultimately lead to reduced fitness and local extinction. Notelaea lloydii is a native olive species endemic to Australia and listed as vulnerable due to its restricted distribution. A recent molecular systematics study has revealed there might be some geographic structuring among N. lloydii populations. Therefore, we undertook a genome-wide single nucleotide polymorphism (SNP) analysis to determine levels and patterns of genetic diversity, inbreeding and gene flow within and among N. lloydii populations in south-eastern Queensland. Furthermore, as the reproductive phase of a plant's life history has a profound influence on genetic diversity, life history reproductive traits were also studied. Our SNP analysis revealed low genetic diversity, inbreeding and significant genetic structuring even among proximate populations. Results of a flower and fruit bagging experiment in two consecutive seasons revealed that N. lloydii produced many flowers but only a few fruits survived to maturity. There were no differences in bagged and un-bagged flowering and fruiting rates, and therefore, we conclude that the high fruit abortion rate was probably due to inbreeding depression and/or suboptimal conditions, rather than pollinator availability and insect attack. Overall, results of this study indicate that the populations of N. lloydii are small, inbred and genetically isolated and represent unique management units that require local conservation management due to ongoing threats associated with urbanisation., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Objectives: This study aimed to evaluate the cost-effectiveness of lung cancer screening (LCS) with volume-based low-dose computed tomography (CT) versus no screening for an asymptomatic high-risk population in the United Kingdom (UK), utilising the long-term insights provided by the NELSON study, the largest European randomized control trial investigating LCS., Methods: A cost-effectiveness analysis was conducted using a decision tree and a state-transition Markov model to simulate the identification, diagnosis, and treatments for a lung cancer high-risk population, from a UK National Health Service (NHS) perspective. Eligible participants underwent annual volume CT screening and were compared to a cohort without the option of screening. Screen-detected lung cancers, costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were predicted., Results: Annual volume CT screening of 1.3 million eligible participants resulted in 96,474 more lung cancer cases detected in early stage, and 73,825 fewer cases in late stage, leading to 53,732 premature lung cancer deaths averted and 421,647 QALYs gained, compared to no screening. The ICER was £5,455 per QALY. These estimates were robust in sensitivity analyses., Limitations: Lack of long-term survival data for lung cancer patients; deficiency in rigorous micro-costing studies to establish detailed treatment costs inputs for lung cancer patients., Conclusions: Annual LCS with volume-based low-dose CT for a high-risk asymptomatic population is cost-effective in the UK, at a threshold of £20,000 per QALY, representing an efficient use of NHS resources with substantially improved outcomes for lung cancer patients, as well as additional societal and economic benefits for society as a whole. These findings advocate evidence-based decisions for the potential implementation of a nationwide LCS in the UK.

People with diabetes feature a life-risking susceptibility to respiratory viral infection, including influenza and SARS-CoV-2 (ref. 1 ), whose mechanism remains unknown. In acquired and genetic mouse models of diabetes, induced with an acute pulmonary viral infection, we demonstrate that hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell (DC) subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality. Mechanistically, hyperglycaemia induces an altered metabolic DC circuitry characterized by increased glucose-to-acetyl-CoA shunting and downstream histone acetylation, leading to global chromatin alterations. These, in turn, drive impaired expression of key DC effectors including central antigen presentation-related genes. Either glucose-lowering treatment or pharmacological modulation of histone acetylation rescues DC function and antiviral immunity. Collectively, we highlight a hyperglycaemia-driven metabolic-immune axis orchestrating DC dysfunction during pulmonary viral infection and identify metabolic checkpoints that may be therapeutically exploited in mitigating exacerbated disease in infected diabetics., (© 2023. The Author(s).)

Feral pigs ( Sus scrofa ) are a destructive and widespread invasive pest in Australia. An understanding of feral pig movement is required to develop management strategies to control feral pigs in Australia. Because landscape structure can have a strong influence on animal movement, it is important to determine how landscape features facilitate or impede the movement of feral pigs. Consequently, we conducted a landscape genetic analysis of feral pig populations in the Herbert region of far north Queensland, Australia, to determine management units and provide recommendations to better inform feral pig population control strategies. Using microsatellite data obtained from 256 feral pig samples from 44 sites, we examined feral pig population structure at multiple spatial scales for univariate and multivariate landscape resistance surfaces to determine the optimal spatial scale and to identify which of the nine landscape features tested impede or facilitate feral pig gene flow. Only weak genetic structure was found among the 44 sampling sites, but major waterways were identified as a minor barrier to gene flow, and an isolation by distance model was supported. We also found that highways facilitated gene flow across the study area, and this suggests that they may act as movement corridors or indicate translocation of feral pigs. Additionally, incorporating a second spatial scale enhanced the ability of our landscape genetics analysis to detect the influence of landscape structure on gene flow. We identified three management units based on natural barriers to gene flow and future targeted control should be undertaken in these management units to deliver sustained reduction of feral pig populations in the Herbert region. This study demonstrates how a landscape genetic approach can be used to gain insight into the ecology of an invasive pest species and be used to develop population control strategies which utilise natural barriers to movement., Competing Interests: The authors declare no competing interests., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Objectives: People suffering from mental health disorder (MHDs) are often under-represented in clinical research though the reasons for their exclusion are rarely recorded. As they have higher rates of smoking and nicotine dependence, it is crucial that they are adequately represented in clinical trials of established pharmacotherapy interventions for smoking cessation. This review aims to examine the practice of excluding smokers with MHDs and reasons for such exclusion in clinical trials evaluating pharmacotherapy treatments for smoking cessation., Data Source: The Cochrane database of systematic reviews was searched until September 2020 for reviews on smoking cessation using pharmacotherapies., Study Selection: Randomised controlled trials (RCTs) within the selected Cochrane reviews were included., Data Extraction: Conducted by one author and independently verified by three authors., Data Synthesis: We included 279 RCTs from 13 Cochrane reviews. Of all studies, 51 (18.3%) explicitly excluded participants with any MHDs, 152 (54.5%) conditionally excluded based on certain MHD criteria and 76 (27.2%) provided insufficient information to ascertain either inclusion or exclusion. Studies of antidepressant medications used for smoking cessation were found to be 3.33 times more likely (95% CI 1.38 to 8.01, p=0.007) to conditionally exclude smokers with MHDs than explicitly exclude compared with studies of nicotine replacement therapy., Conclusion: Smokers with MHDs are not sufficiently represented in RCTs examining the safety and effectiveness of smoking cessation medications. Greater access to clinical trial participation needs to be facilitated for this group to better address access to appropriate pharmacotherapeutic interventions in this vulnerable population., Competing Interests: Competing interests: HM has received honoraria for speaking at smoking cessation meetings and attending advisory board meetings that have been organised by Pfizer. SRT, JML, VB and RJC have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We prospectively assessed the ability of a novel transurethral catheterization safety valve to prevent urethral catheter balloon injury in a multi-institutional clinical setting., Materials and Methods: A prospective, multi-institution study was conducted. The safety valve was introduced for urinary catheterization in 6 hospital groups (4 in Ireland; 2 in the UK). The safety valve allows fluid in the catheter system to vent through a pressure relief valve if attempted intraurethral inflation of the catheter's anchoring balloon occurs. Device usage was studied over a 12-month period, with data recorded using a 7-item data sticker containing a scannable QR code. "Venting" through the safety valve during catheterization was indicative of prevention of a urethral injury. An embedded 3-month study was conducted in 3 centers, with any catheter balloon injuries occurring during catheterization without safety valve use referred to the on-call urology team recorded. Health economic analyses were also performed., Results: During the overall 12-month device study phase, 994 urethral catheterizations were performed across study sites. Twenty-two (2.2%) episodes of safety valve venting were recorded. No urethral injuries occurred in these patients. In the embedded 3-month study, 18 catheter balloon injuries were recorded in association with catheterizations performed without the safety valve. Based on confirmed and device-prevented urethral injuries, the injury rate for urethral catheterization without safety valve use was calculated to be 5.5/1,000 catheterizations., Conclusions: The safety valve has the potential to eliminate catheter balloon injury if widely adopted. It represents a simple, effective, and innovative solution to this recurring problem applicable to all patient cohorts.

Involvement of all relevant stakeholders will be of utmost importance for the success of the developing EU HTA harmonization process. A multi-step procedure was applied to develop a survey across stakeholders/collaborators within the EU HTA framework to assess their current level of involvement, determine their suggested future role, identify challenges to contribution, and highlight efficient ways to fulfilling their role. The 'key' stakeholder groups identified and covered by this research included: patients', clinicians', regulatory, and Health Technology Developer representatives. The survey was circulated to a wide expert audience including all relevant stakeholder groups in order to determine self-perception by the 'key' stakeholders regarding involvement in the HTA process (self-rating), and in a second, slightly modified version of the questionnaire, to determine the perception of 'key' stakeholder involvement by HTA bodies, payers, and policymakers (external rating). Predefined analyses were conducted on the submitted responses. Fifty-four responses were received (patients 9; clinicians: 8; regulators: 4; HTDs 14; HTA bodies: 7; Payers: 5; policymakers 3; others 4). The mean self-perceived involvement score was consistently lower for each of the 'key' stakeholder groups than the respective external ratings. Based on the qualitative insights generated in the survey, a RACI Chart (Responsible/Accountable/Consulted/Informed) was developed for each of the stakeholder groups to determine their roles and involvement in the current EU HTA process. Our findings suggest extensive effort and a distinct research agenda are required to ensure adequate involvement of the key stakeholder groups in the evolving EU HTA process., Competing Interests: The views expressed in this article are the personal views of the author(s) and may not be understood or quoted as being made on behalf of or reflecting the position of the regulatory agency/agencies or organizations with which the author(s) is/are employed/affiliated., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Projecting the effects of climate change on net reef calcium carbonate production is critical to understanding the future impacts on ecosystem function, but prior estimates have not included corals' natural adaptive capacity to such change. Here we estimate how the ability of symbionts to evolve tolerance to heat stress, or for coral hosts to shuffle to favourable symbionts, and their combination, may influence responses to the combined impacts of ocean warming and acidification under three representative concentration pathway (RCP) emissions scenarios (RCP2.6, RCP4.5 and RCP8.5). We show that symbiont evolution and shuffling, both individually and when combined, favours persistent positive net reef calcium carbonate production. However, our projections of future net calcium carbonate production (NCCP) under climate change vary both spatially and by RCP. For example, 19%-35% of modelled coral reefs are still projected to have net positive NCCP by 2050 if symbionts can evolve increased thermal tolerance, depending on the RCP. Without symbiont adaptive capacity, the number of coral reefs with positive NCCP drops to 9%-13% by 2050. Accounting for both symbiont evolution and shuffling, we project median positive NCPP of coral reefs will still occur under low greenhouse emissions (RCP2.6) in the Indian Ocean, and even under moderate emissions (RCP4.5) in the Pacific Ocean. However, adaptive capacity will be insufficient to halt the transition of coral reefs globally into erosion by 2050 under severe emissions scenarios (RCP8.5)., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Background: Pulmonary nodule growth is often measured by volume doubling time (VDT), which may guide management. Most malignant nodules have a VDT of 20 to 400 days, with longer VDTs typically observed in indolent nodules. We assessed the utility of VDT in differentiating pulmonary carcinoids and hamartomas., Methods: A review was performed from January 2012 to October 2021 to identify patients with pathologic diagnoses and at least 2 chest computed tomography scans obtained 6 or more months apart. Visualization software was used to segment nodules and calculate diameter and volume. Volume doubling time was calculated for scans with 1-mm slices. For the remainder, estimated nodule volume doubling time (eVDT) was calculated using nodule diameter. Volume doubling times/eVDTs were placed into growth categories: less than 400 days; 400-600 days; and more than 600 days., Results: Sixty nodules were identified, 35 carcinoids and 25 hamartomas. Carcinoids were larger than hamartomas (median diameter, 13.5 vs 11.5 mm; P = 0.05). For carcinoid tumors, median VDT (n = 15) was 1485 days, and median eVDT (n = 32) was 1309 days; for hamartomas, median VDT (n = 8) was 2040 days and median eVDT (n = 25) was 2253 days. Carcinoid tumor eVDT was significantly shorter than hamartomas ( P = 0.03). By growth category, 1 of 25 hamartomas and 5 of 35 carcinoids had eVDT less than 400 days and 24 of 25 hamartomas and 27 of 35 carcinoids had eVDT more than 600 days. Of 4 carcinoid tumors with metastases, 2 had eVDT less than 400 days and 2 had eVDT more than 600 days., Conclusions: Growth rate was not a reliable differentiator of pulmonary hamartomas and carcinoids. Slow growing carcinoids can metastasize. Radiologists should be cautious when discontinuing computed tomography follow-up based on growth rates alone., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Unlike other nucleotide oligomerization domain-like receptors, Nlrp10 lacks a canonical leucine-rich repeat domain, suggesting that it is incapable of signal sensing and inflammasome formation. Here we show that mouse Nlrp10 is expressed in distal colonic intestinal epithelial cells (IECs) and modulated by the intestinal microbiome. In vitro, Nlrp10 forms an Apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC)-dependent, m-3M3FBS-activated, polyinosinic:polycytidylic acid-modulated inflammasome driving interleukin-1β and interleukin-18 secretion. In vivo, Nlrp10 signaling is dispensable during steady state but becomes functional during autoinflammation in antagonizing mucosal damage. Importantly, whole-body or conditional IEC Nlrp10 depletion leads to reduced IEC caspase-1 activation, coupled with enhanced susceptibility to dextran sodium sulfate-induced colitis, mediated by altered inflammatory and healing programs. Collectively, understanding Nlrp10 inflammasome-dependent and independent activity, regulation and possible human relevance might facilitate the development of new innate immune anti-inflammatory interventions., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Patient evaluations of their physician have been utilized to evaluate physician performance and calculate hospital reimbursement. Despite the routine use of these evaluations, little research has been done to evaluate the accuracy of these evaluations. We assessed patient's ability to correctly identify the hospitalist providing their care and whether identification of the hospitalist affected the cumulative satisfaction scores. Methods: This prospective observational study was conducted at a suburban voluntary hospital. Hospitalists were evaluated anonymously by their patients over a 4-month period on a questionnaire designed to assess patient satisfaction. Results: One hundred fifty-eight patients evaluated 16 hospitalists yielding an average of 9.9 evaluations per hospitalist. Forty Nine (31%) patients were able to identify their hospitalist. The top score (3) accounted for 76% of patient responses across all questions. Significant differences ( p = .0007) existed in the distribution of these scores when patients who could identify their hospitalist was compared with those who couldn't. The variables for effective communication and hospitalist introduction were scored significantly higher by patients who could identify their hospitalist (2.77 vs 2.55; p = .027 and 2.90 vs 2.67; p = .005). Patients of younger age and female gender were more likely identify their hospitalist. Conclusions: Less than one-third of patients were able to correctly identify their hospitalist. The variables for effective communication and hospitalist introduction to the patient were scored significantly higher by patients who could identify their hospitalist. The elimination of scores by patients who could not correctly identify their provider resulted in marked changes in the percentile ranking of these providers.

Over the past 4 years, the authors have participated as members of the Mobilizing Computable Biomedical Knowledge Technical Infrastructure working group and focused on conceptualizing the infrastructure required to use computable biomedical knowledge. Here, we summarize our thoughts and lay the foundation for future work in the development of CBK infrastructure, including: explaining the difference between computable knowledge and data, and contextualizing the conversation with the Learning Health Systems and the FAIR principles. Specifically, we provide three guiding principles to advance the development of CBK infrastructure: (a) Promote interoperable systems for data and knowledge to be findable, accessible, interoperable, and reusable. (b) Enable stable, trustworthy knowledge representations that are human and machine readable. (c) Computable knowledge resources should, when possible, be open. Standards supporting computable knowledge infrastructures must be open., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Learning Health Systems published by Wiley Periodicals LLC on behalf of University of Michigan.)

Fear generalization is a conserved survival mechanism that can become maladaptive in the face of traumatic situations, a feature central to certain anxiety disorders including posttraumatic stress disorder (PTSD). However, the neural circuitry and molecular mechanisms underlying fear generalization remain unclear. Recent studies have shown that prophylactic treatment with (R,S)-ketamine confers protective effects in stress-induced depressive behaviors and enhances contextual fear discrimination, but the extent to which these effects extend to fear generalization after auditory fear conditioning remains unclear. Here, we build on this work by using a behavioral model of fear generalization in mice involving foot shocks with differential intensity levels during auditory fear conditioning. We find that prophylactic (R,S)-ketamine treatment exerts protective effects that results in enhanced fear discrimination in wild type mice. As the growth factor, brain-derived neurotrophic factor (BDNF), has been shown to mediate the rapid antidepressant actions of (R,S)-ketamine, we used a loss-of-function BDNF mouse line (BDNF Val66Met) to determine whether BDNF is involved in (R,S)-ketamine's prophylactic effects on fear generalization. We found that BDNF Val66Met mice were resistant to the protective effects of prophylactic (R,S)-ketamine administration on fear generalization and extinction. We then used fiber photometry to parse out underlying neural activity and found that in the ventral hippocampus there were significant fear generalization-dependent patterns of activity for wild type and BDNF Val66Met mice that were altered by prophylactic (R,S)-ketamine treatment. Overall, these findings indicate a role for the ventral hippocampus and BDNF signaling in modulating the mitigating effects of prophylactic (R,S)-ketamine treatment on generalized fear., (© 2022. The Author(s).)

Introduction: Imipenem/cilastatin/relebactam (IMI/REL), a combination β-lactam antibiotic (imipenem) with a novel β-lactamase inhibitor (relebactam), is an efficacious and well-tolerated option for the treatment of hospitalized patients with gram-negative (GN) bacterial infections caused by carbapenem-non-susceptible (CNS) pathogens. This study examines cost-effectiveness of IMI/REL vs. colistin plus imipenem (CMS + IMI) for the treatment of infection(s) caused by confirmed CNS pathogens., Methods: We developed an economic model comprised of a decision-tree depicting initial hospitalization, and a Markov model projecting long-term health and economic impacts following discharge. The decision tree, informed by clinical data from RESTORE-IMI 1 trial, modeled clinical outcomes (mortality, cure rate, and adverse events including nephrotoxicity) in the two comparison scenarios of IMI/REL versus CMS + IMI for patients with CNS GN infection. Subsequently, a Markov model translated these hospitalization stage outcomes (i.e., death or uncured infection) to long-term consequences such as quality-adjusted life years (QALYs). Sensitivity analyses were conducted to test the model robustness., Results: IMI/REL compared to CMS + IMI demonstrated a higher cure rate (79.0% vs. 52.0%), lower mortality (15.2% vs. 39.0%), and reduced nephrotoxicity (14.6% vs. 56.4%). On average a patient treated with IMI/REL vs. CMS + IMI gained additional 3.7 QALYs over a lifetime. Higher drug acquisition costs for IMI/REL were offset by shorter hospital length of stay and lower AE-related costs, which result in net savings of $11,015 per patient. Sensitivity analyses suggested that IMI/REL has a high likelihood (greater than 95%) of being cost-effective at a US willingness-to-pay threshold of $100,000-150,000 per QALY., Conclusions: For patients with confirmed CNS GN infection, IMI/REL could yield favorable clinical outcomes and may be cost-saving-as the higher IMI/REL drug acquisition cost is offset by reduced nephrotoxicity-related cost-for the US payer compared to CMS + IMI., (© 2022. The Author(s).)

Purpose: Prolonged ureteroscopy (URS) is associated with complications including ureteral perforation, stricture, and urosepsis. As laser lithotripsy is one of the most common urologic procedures, small cost savings per case can have a large financial impact. This retrospective study was designed to determine if Thulium fiber laser (TFL) lithotripsy decreases operative time and costs compared to standard Holmium:YAG (Ho:YAG) lithotripsy without pulse modulation., Methods: A retrospective review of URS with laser lithotripsy was conducted for 152 cases performed from August 2020 to January 2021. Variables including cumulative stone size, location, chemical composition, prior ureteral stenting, and ureteral access sheath use were recorded for each case. A cost benefit analysis was performed to show projected cost savings due to potentially decreased operative times., Results: Compared to Ho:YAG, use of TFL resulted in an average decrease of 12.9 min per case (p = .021, 95% CI [2.03-23.85]). In subgroup analysis of cases with cumulative stone diameter less than 15 mm, the difference was 14.0 min (p = .007, CI [3.95-23.95]). For cases less than 10 mm, the mean difference was 17.3 min in favor of TFL (p = .002, 95% CI [6.89-27.62]). This ~ 13 min reduction in operative time resulted in saving $440/case in direct operating room costs giving our institution a range of $294,000 to $381,900 savings per year., Conclusions: TFL has a significantly shorter operative time and decreased cost when compared to the standard Ho:YAG for equivalent kidney stone and patient characteristics. Longer term follow up is needed to see if recurrence rates are affected., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cells can crawl, self-heal, and tune their stiffness due to their remarkably dynamic cytoskeleton. As such, reconstituting networks of cytoskeletal biopolymers may lead to a host of active and adaptable materials. However, engineering such materials with precisely tuned properties requires measuring how the dynamics depend on the network composition and synthesis methods. Quantifying such dynamics is challenged by variations across the time, space, and formulation space of composite networks. The protocol here describes how the Fourier analysis technique, differential dynamic microscopy (DDM), can quantify the dynamics of biopolymer networks and is particularly well suited for studies of cytoskeleton networks. DDM works on time sequences of images acquired using a range of microscopy modalities, including laser-scanning confocal, widefield fluorescence, and brightfield imaging. From such image sequences, one can extract characteristic decorrelation times of density fluctuations across a span of wave vectors. A user-friendly, open-source Python package to perform DDM analysis is also developed. With this package, one can measure the dynamics of labeled cytoskeleton components or of embedded tracer particles, as demonstrated here with data of intermediate filament (vimentin) networks and active actin-microtubule networks. Users with no prior programming or image processing experience will be able to perform DDM using this software package and associated documentation.

Intestinal macrophages play a vital role in the maintenance of gut homeostasis through signals derived from the microbiota. We previously demonstrated that microbial-derived metabolites can shape the metabolic functions of macrophages. Here, we show that antibiotic-induced disruption of the intestinal microbiota dramatically alters both the local metabolite environment and the metabolic functions of macrophages in the colon. Broad-spectrum antibiotic administration in mice increased the expression of the large neutral amino acid transporter LAT1 and accordingly, amino acid uptake. Subsequently, antibiotic administration enhanced the metabolic functions of colonic macrophages, increasing phosphorylation of components of mammalian/mechanistic target of rapamycin signalling pathways, with increased expression of genes involved in glycolysis and oxidative phosphorylation (OXPHOS), increased mitochondrial function, increased rate of extracellular acidification (ECAR; measure of glycolysis) and increased rate of oxygen consumption (OCR; measure of OXPHOS). Small bowel macrophages were less metabolically active than their colonic counterparts, with macrophage metabolism in the small intestine being independent of the microbiota. Finally, we reveal tissue-resident Tim4 +  CD4 + macrophages exhibit enhanced fatty acid uptake alongside reduced fatty acid synthesis compared to recruited macrophages. Thus, the microbiota shapes gut macrophage metabolism in a compartment-specific manner, with important implications for monocyte recruitment and macrophage differentiation., (© 2022 The Authors. Immunology published by John Wiley & Sons Ltd.)

The use of face masks has increased dramatically since the COVID-19 pandemic started in order to to curb the spread of the disease. Additionally, breakthrough infections caused by the Delta and Omicron variants have further increased the importance of wearing a face mask, even for vaccinated individuals. However, the use of face masks also induces attenuation in speech signals, and this change may impact speech processing technologies, e.g., automated speaker verification (ASV) and speech to text conversion. In this paper we examine Automatic Speaker Verification (ASV) systems against the speech samples in the presence of three different types of face mask: surgical, cloth, and filtered N95, and analyze the impact on acoustics and other factors. In addition, we explore the effect of different microphones, and distance from the microphone, and the impact of face masks when speakers use ASV systems in real-world scenarios. Our analysis shows a significant deterioration in performance when an ASV system encounters different face masks, microphones, and variable distance between the subject and microphone. To address this problem, this paper proposes a novel framework to overcome performance degradation in these scenarios by realigning the ASV system. The novelty of the proposed ASV framework is as follows: first, we propose a fused feature descriptor by concatenating the novel Ternary Deviated overlapping Patterns (TDoP), Mel Frequency Cepstral Coefficients (MFCC), and Gammatone Cepstral Coefficients (GTCC), which are used by both the ensemble learning-based ASV and anomaly detection system in the proposed ASV architecture. Second, this paper proposes an anomaly detection model for identifying vocal samples produced in the presence of face masks. Next, it presents a Peak Norm (PN) filter to approximate the signal of the speaker without a face mask in order to boost the accuracy of ASV systems. Finally, the features of filtered samples utilizing the PN filter and samples without face masks are passed to the proposed ASV to test for improved accuracy. The proposed ASV system achieved an accuracy of 0.99 and 0.92, respectively, on samples recorded without a face mask and with different face masks. Although the use of face masks affects the ASV system, the PN filtering solution overcomes this deficiency up to 4%. Similarly, when exposed to different microphones and distances, the PN approach enhanced system accuracy by up to 7% and 9%, respectively. The results demonstrate the effectiveness of the presented framework against an in-house prepared, diverse Multi Speaker Face Masks (MSFM) dataset, (IRB No. FY2021-83), consisting of samples of subjects taken with a variety of face masks and microphones, and from different distances.

Background and Aims: The learning curve for robotic-assisted radical prostatectomy (RARP) is estimated to be about 50-200 cases. This study will evaluate the benefit of a mentorship programme after completing a mini-fellowship in RARP by an experienced surgeon who previously trained in open and laparoscopic surgery., Methods: Our study was a retrospective comparative analysis of RARP performed by a single consultant urologist. A retrospective chart review of the first 120 cases was performed. The 120 patients were divided into three groups of 40 cases. For the first 40 cases, an appropriately qualified mentor was present. The peri-operative and oncological outcomes were compared between the three groups., Results: Operative times significantly decreased with experience (250 min vs 234 min vs 225 min, p < 0.05). Complication rates, estimated blood loss, and length of stay were similar between all groups. There was a higher rate of positive margins in the final group (20% vs 17.5% vs 32.5%, p < 0.5). There was a greater number of pT3 tumours in group 3 (42%, n = 17) compared to groups 1 and 2 (20%, n = 8, and 22.5%, n = 9) which may account for the higher rate of positive margins in this group., Conclusion: In the transition of an experienced laparoscopic surgeon to robotic surgery, we showed that there is a benefit of a mentorship programme after a mini-fellowship in reducing the impact of the learning curve on patient outcomes. Ongoing mentorship may be of benefit in cases where a high volume of tumour is suspected and should be avoided in the early part of the learning curve to maximise oncological outcomes., (© 2021. Royal Academy of Medicine in Ireland.)

Introduction: The 2019 novel coronavirus pandemic has caused significant disruptions in the clinical operations of hospitals as well as clinical education, training, and research at academic centers. New York State was among the first and largest epicenters of the pandemic, resulting in significant disruptions across its 29 emergency medicine (EM) residency programs. We conducted a cross-sectional observational study of EM residency programs in New York State to assess the impact of the pandemic on resident education and training programs., Methods: We surveyed a cross-sectional sample of residency programs throughout New York State in June 2020, in the timeframe immediately after the state's first "wave" of the pandemic. The survey was distributed to program leadership and elicited information on pandemic-prompted curricular modifications and other educational changes. The survey covered topics related to disruptions in medical education and sought details on solutions to educational issues encountered by programs., Results: Of the 29 accredited EM residency programs in New York State, leadership from 22 (76%) responded. Of these participating programs, 11 (50%) experienced high pandemic impact on clinical services, 21 (95%) canceled their own trainees' off-service rotations, 22 (100%) canceled or postponed visiting medical student rotations, 22 (100%) adopted virtual conference formats (most within the first week of the pandemic wave), and 11 (50%) stopped all prospective research (excluding COVID-19 research), while most programs continued retrospective research., Conclusion: This study highlights the profound educational impact of the pandemic on residency programs in one of the hardest- and earliest-hit regions in the United States. Specifically, it highlights the ubiquity of virtual conferencing, the significant impact on research, and the concerns about canceled rotations and missed training opportunities for residents, as well as prehospital and non-physician practitioner trainees. This data should be used to prompt discussion regarding the necessity of alternate educational modalities for pandemic times and the sequelae of implementing these plans.

Shuttle catalysis has emerged as a useful methodology for the reversible transfer of small functional groups, such as CO and HCN, and goes far beyond transfer hydrogenation chemistry. While a biocatalytic hydrogen-borrowing methodology is well established, the biocatalytic borrowing of alternative functional groups has not yet been realized. Herein, we present a new concept of amine borrowing via biocatalytic shuttle catalysis, which has no counterpart in chemo-shuttle catalysis and allows efficient intermolecular amine shuttling to generate reactive intermediates in situ . By coupling this dynamic exchange with an irreversible downstream step to displace the reaction equilibrium in the forward direction, high conversion to target products can be achieved. We showcase the potential of this amine-borrowing methodology using a biocatalytic equivalent of both the Knorr-pyrrole synthesis and Pictet-Spengler reaction.

Epilepsy is a common neurological disorder affecting over 50 million people worldwide. Although more than 20 new anti-seizure medications have been developed in the past three decades, about one-third of patients still experience recurrent seizures. The heterogeneity of epilepsy types and the highly variable inter-individual response to the therapies makes disease management challenging. A precision medicine approach of treatment for epilepsy patients that considers individual patient characteristics has long been advocated. With advances in DNA sequencing technology, it has been estimated than >30% of all epilepsy syndromes have genetic components. Here we summarize recent approaches in genetic testing and current personalized treatments that are already applicable in genetic epilepsy syndromes. We also discuss current precision therapy utilized in personalized pharmacogenomics, as well as tailored treatment with neuromodulation for epilepsy patients. In the near future, we envision precision medicine in epilepsy will be applicable on a large scale involving not only targeted therapies, but also diagnosis, prognosis, and comorbidity management., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To examine the incidence of surgical site complications associated with pronation-abduction ankle fracture-dislocations with an open medial tension wound., Design: Retrospective case series., Setting: Accredited Level-1 trauma center., Patients/participants: Forty-eight open pronation-abduction ankle fracture-dislocations with medial tension failure wounds treated at our institution from 2014 to 2016., Intervention: Immediate irrigation and debridement along with surgical stabilization of open ankle fracture-dislocation., Main Outcome Measures: The primary outcome measure was deep surgical site infection. Secondary outcome measures included other surgical site complications and adverse radiographic events., Results: A total of 5 patients (10.4%) developed a deep surgical site infection requiring additional surgical debridement. One of the patients with a deep surgical site infection required a below-knee amputation as a result of sepsis. Adverse radiographic outcomes included 3 fibular nonunions (6.3%), 3 implant failures related to syndesmotic fixations (6.3%), one periimplant fracture (2.1%), and postoperative collapse of the tibial plafond in 3 patients (6.3%)., Conclusions: Open pronation-abduction ankle fracture-dislocations with medial tension failure wounds remain a challenging and potentially devastating injury. Our study suggests that with appropriate surgical debridement, early stabilization, and primary wound closure, acceptable outcomes with a relatively low risk of surgical site complications can be achieved., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: B. A. Zelle has consulted for KCI Inc. USA and DepuySynthes and received compensation. B. A. Zelle has also received speaker fees from AO North America. B. A. Zelle has received research grants from DepuySynthes, KCI Inc. USA, Department of Defense, and the Orthopaedic Trauma Association. B. A. Zelle has received educational grants from COTA, Smith and Nephew Inc. and Arthrex. He serves on the editorial board of International Orthopaedics, Journal of Bone and Joint Surgery, Journal of Orthopaedic Trauma, and Patient Safety in Surgery. The remaining authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This paper aims to determine whether a single session of a motivational interview (MI) reduces smoking relapse amongst people released from smoke-free prisons., Design/methodology/approach: This study sought to recruit 824 ex-smokers from 2 smoke-free prisons in the Northern Territory, Australia. Participants were randomised to receive either one session (45-60 min) face-to-face MI intervention 4-6 weeks prior to release or usual care (UC) without smoking advice. The primary outcome was continuous smoking abstinence verified by exhaled carbon monoxide test (<5 ppm) at three months post-release. Secondary outcomes included seven-day point-prevalence, time to the first cigarette and the daily number of cigarettes smoked after release., Findings: From April 2017 to March 2018, a total of 557 participants were randomised to receive the MI ( n  = 266) or UC ( n  = 291), with 75% and 77% being followed up, respectively. There was no significant between-group difference in continuous abstinence (MI 8.6% vs UC 7.4%, risk ratio = 1.16, 95%CI 0.67∼2.03). Of all participants, 66.9% relapsed on the day of release and 90.2% relapsed within three months. On average, participants in the MI group smoked one less cigarette daily than those in the UC within the three months after release ( p  < 0.01)., Research Limitations/implications: A single-session of MI is insufficient to reduce relapse after release from a smoke-free prison. However, prison release remains an appealing time window to build on the public health benefit of smoke-free prisons. Further research is needed to develop both pre- and post-release interventions that provide continuity of care for relapse prevention., Originality/value: This study is the first Australian randomised controlled trial to evaluate a pre-release MI intervention on smoking relapse prevention amongst people released from smoke-free prisons., (© Emerald Publishing Limited.)

Introduction: Varicocele is a relatively common condition in men that causes pain in approximately 10% of cases. There have been few studies to date assessing the improvements in both pain and quality of life parameters associated with spermatic vein embolization (SVE) as a treatment for patients with symptomatic varicocele, so we aimed to assess this., Methods: A review was carried out of consecutive SVE procedures performed at our institution from 2013-2019. Only patients with painful varicocele were included after other causes of testicular pain were excluded. The technique employed was a combination of distal coil embolization of the spermatic vein with 4-6 mm coils at the level of the inguinal canal, as well as sclerotherapy to prevent reflux of sclerosant. Furthermore, a prospective validated Pain Impact Questionnaire-6 (PIQ-6) was performed to assess for improvement in quality of life. A matched pair Student two-tailed t-test was used to compare mean scores pre- and post-treatment, with 95% confidence intervals presented as T scores and their associated p-values., Results: Over six years, 62 SVE procedures were performed for symptomatic varicocele. Success rate was 95%, with a median followup of nine months. Two patients had a failed procedure on two occasions requiring subsequent surgical ligation. There was one clinically significant recurrence. All components of PIQ-6 score showed a statistically significant reduction post-SVE, most noticeably pain severity and impact on leisure activities., Conclusions: SVE is a safe, effective, and well-tolerated treatment for symptomatic varicocele, improving pain and quality of life.

Background: Providing digital recordings of clinic visits to patients has emerged as a strategy to promote patient and family engagement in care. With advances in natural language processing, an opportunity exists to maximize the value of visit recordings for patients by automatically tagging key visit information (eg, medications, tests, and imaging) and linkages to trustworthy web-based resources curated in an audio-based personal health library., Objective: This study aims to report on the user-centered development of HealthPAL, an audio personal health library., Methods: Our user-centered design and usability evaluation approach incorporated iterative rounds of video-recorded sessions from 2016 to 2019. We recruited participants from a range of community settings to represent older patient and caregiver perspectives. In the first round, we used paper prototypes and focused on feature envisionment. We moved to low-fidelity and high-fidelity versions of the HealthPAL in later rounds, which focused on functionality and use; all sessions included a debriefing interview. Participants listened to a deidentified, standardized primary care visit recording before completing a series of tasks (eg, finding where a medication was discussed in the recording). In the final round, we recorded the patients' primary care clinic visits for use in the session. Findings from each round informed the agile software development process. Task completion and critical incidents were recorded in each round, and the System Usability Scale was completed by participants using the digital prototype in later rounds., Results: We completed 5 rounds of usability sessions with 40 participants, of whom 25 (63%) were women with a median age of 68 years (range 23-89). Feedback from sessions resulted in color-coding and highlighting of information tags, a more prominent play button, clearer structure to move between one's own recordings and others' recordings, the ability to filter recording content by the topic discussed and descriptions, 10-second forward and rewind controls, and a help link and search bar. Perceived usability increased over the rounds, with a median System Usability Scale of 78.2 (range 20-100) in the final round. Participants were overwhelmingly positive about the concept of accessing a curated audio recording of a clinic visit. Some participants reported concerns about privacy and the computer-based skills necessary to access recordings., Conclusions: To our knowledge, HealthPAL is the first patient-centered app designed to allow patients and their caregivers to access easy-to-navigate recordings of clinic visits, with key concepts tagged and hyperlinks to further information provided. The HealthPAL user interface has been rigorously co-designed with older adult patients and their caregivers and is now ready for further field testing. The successful development and use of HealthPAL may help improve the ability of patients to manage their own care, especially older adult patients who have to navigate complex treatment plans., (©Paul J Barr, William Haslett, Michelle D Dannenberg, Lisa Oh, Glyn Elwyn, Saeed Hassanpour, Kyra L Bonasia, James C Finora, Jesse A Schoonmaker, W Moraa Onsando, James Ryan, Martha L Bruce, Amar K Das, Roger Arend, Sheryl Piper, Craig H Ganoe. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.10.2021.)

Introduction: The use of multiparametric magnetic resonance imaging (MRI) with targeted biopsies of the prostate improves the diagnosis of clinically significant prostate cancer. Recent studies have shown that targeted prostate biopsies also more accurately predict final histopathology after radical prostatectomy (RP). There are three broad techniques for performing MRI-targeted prostate biopsy: cognitive MRI/ultrasound (US) fusion, software MRI/US fusion, and in-bore MRI-guided. Current practices recommend that a standard systematic 12-core prostate biopsy be performed, as well as targeted biopsies in patients with positive MRI findings. This study aimed to evaluate the accuracy of histological grading of cognitive MRI/US fusion prostate biopsy by comparing the histology from the targeted biopsy specimens (TB), standard systematic specimens (SB), and the combination of both (CB) specimens with the final histological grade from subsequent prostatectomy., Methods: A retrospective, single-center review of 115 patients who underwent standard systematic and cognitive MRI/US-targeted biopsy of the prostate before undergoing a RP between 2016 and 2019 was performed. MRI findings, biopsy, final histology International Society of Urological Pathology (ISUP) grades, and patient demographics were collected. Cochran's Q test and McNemar test were used to compare the differences in upgrading, downgrading, and concordance between each biopsy group., Results: The concordance between SB, TB, and CB biopsy were 28.7%, 49.6%, and 50.4%, respectively. There was no significant difference in concordance between TB and CB. Patients were more likely to be downgraded on the final histology when comparing CB with TB alone (26.1% vs. 16.5%, p<0.05). In cases where an ISUP grade 1 cancer was diagnosed on TB (n=24), there was a 62.5% chance that the final histology would be upgraded. In the same sample, when combined with a SB, the risk of upgrading on final histology was reduced to 37.5%., Conclusions: Although grading concordance between TB and CB were similar, the concomitant use of a SB significantly reduced the rate of upgrading in the final RP histopathology. CB may result in better decision-making regarding treatment options and also have implications for intraoperative planning.

Objectives: The objective of this study is to build and evaluate a natural language processing approach to identify medication mentions in primary care visit conversations between patients and physicians., Materials and Methods: Eight clinicians contributed to a data set of 85 clinic visit transcripts, and 10 transcripts were randomly selected from this data set as a development set. Our approach utilizes Apache cTAKES and Unified Medical Language System controlled vocabulary to generate a list of medication candidates in the transcribed text and then performs multiple customized filters to exclude common false positives from this list while including some additional common mentions of the supplements and immunizations., Results: Sixty-five transcripts with 1121 medication mentions were randomly selected as an evaluation set. Our proposed method achieved an F-score of 85.0% for identifying the medication mentions in the test set, significantly outperforming existing medication information extraction systems for medical records with F-scores ranging from 42.9% to 68.9% on the same test set., Discussion: Our medication information extraction approach for primary care visit conversations showed promising results, extracting about 27% more medication mentions from our evaluation set while eliminating many false positives in comparison to existing baseline systems. We made our approach publicly available on the web as an open-source software., Conclusion: Integration of our annotation system with clinical recording applications has the potential to improve patients' understanding and recall of key information from their clinic visits, and, in turn, to positively impact health outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Historically, the standard of care for patients with unresectable, Stage III non-small cell lung cancer had been concurrent chemoradiotherapy. However, outcomes had been poor, with approximately 15% to 32% of patients alive at 5 years. In the placebo-controlled Phase III A PACIFIC trial, consolidation treatment with durvalumab after concurrent chemoradiotherapy significantly improved overall survival (OS) and progression-free survival in patients with unresectable, Stage III non-small cell lung cancer, establishing this regimen as a new standard of care in this setting. In the PACIFIC trial, crossover between treatment arms (durvalumab or placebo) was not permitted. However, after discontinuation from study treatment, patients from both arms of PACIFIC could switch to subsequent anticancer therapy, including durvalumab and other immunotherapies, which is known to influence standard intention-to-treat analysis of OS, potentially underestimating the effect of an experimental drug. Moreover, the introduction of immunotherapies has demonstrated marked improvements in the postprogression, metastatic non-small cell lung cancer setting., Objective: To examine the influence of subsequent immunotherapy on OS in the PACIFIC trial., Methods: Both a Rank Preserving Structural Failure Time Model (RPSFTM) and modified 2-stage method were used. RPSFTM assumes that a patient's survival time with no immunotherapy (counterfactual survival time) is equal to the observed time influenced by immunotherapy, multiplied by an acceleration factor, plus the time not influenced. The modified 2-stage method estimates the effect of immunotherapy by comparing postsubsequent-treatment-initiation survival times between patients with and without subsequent immunotherapy. In both models, OS was adjusted to reflect a hypothetical scenario in which no patients received subsequent immunotherapy. RPSFTM was also used for scenarios in which subsequent immunotherapy was received by increasing proportions of placebo patients but none of the durvalumab patients., Results: In the intention-to-treat analysis (3-year follow-up), durvalumab improved OS versus placebo (stratified hazard ratio = 0.69; 95% CI, 0.55-0.86). Overall, 10% and 27% of durvalumab and placebo patients, respectively, received subsequent immunotherapy. With subsequent immunotherapy removed from both arms, estimated hazard ratio was 0.66 (95% CI, 0.53-0.84) with RPSFTM and 0.68 (95% CI, 0.54-0.85) with the modified 2-stage method. With subsequent immunotherapy removed from the durvalumab arm only (RPSFTM), estimated hazard ratio increased as the proportion of placebo patients receiving subsequent immunotherapy increased, up to 0.75 (95% CI, 0.60-0.94) maximum (assuming all placebo patients with subsequent treatment received immunotherapy)., Conclusions: Results were consistent with the intention-to-treat analysis, supporting the conclusion that durvalumab after chemoradiotherapy provides substantial OS benefit in patients with Stage III, unresectable non-small cell lung cancer. ClinicalTrials.gov identifier: NCT02125461 (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX)., (© 2021 The Author(s).)

Purpose: The purpose of this study was to conduct a comprehensive systematic review and meta-analysis to investigate the clinical and imaging outcomes of all 4 types of platelet-rich therapies (pure platelet-rich plasma [P-PRP], leukocyte and platelet-rich plasma, pure platelet-rich fibrin, and leukocyte and platelet-rich fibrin) in rotator cuff repairs., Methods: A systematic literature search was performed to identify rotator cuff tears comparing any of the 4 types of platelet-rich products (PRP) to a control in rotator cuff repair. Data extracted from the studies included retear rates diagnosed with imaging studies, as well as outcome scores such as Constant, American Shoulder and Elbow Surgeons (ASES), University of California Los Angeles (UCLA), Simple Shoulder Test (SST), and visual analog scale (VAS). Meta-analyses compared postoperative outcome scores and retear rates between the control and study groups., Results: Seventeen studies were included in the meta-analysis. When pooling data from all studies, retear rate for the treatment group was 19.3%, compared to 25.4% for the control group (odds ratio [OR] 0.59, P = .0037). When stratified based on PRP type, only P-PRP resulted in a significant reduction in retear rate (OR 0.26, P = .0005). Overall, treatment with PRP significantly improved Constant scores when compared to controls (mean difference [MD] 2.41, P =.0027), as well as VAS scores (MD -0.12, P = .0014), and SST scores (MD 0.41, P = .0126). There was no significant difference in ASES scores (MD 0.37, P = .7762) or UCLA scores (MD 0.76, P =0.2447) between treatment and controls when pooling data from all studies., Conclusions: This analysis demonstrates significant reductions in retear rates when rotator cuff repair is augmented with PRP. P-PRP appears to be the most effective formulation, resulting in significantly improved retear rates and clinical outcome scores when compared with controls., (Copyright © 2021 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Summary: Distal radius fractures are one of the most common fractures seen in orthopaedics. These fractures may be treated surgically or conservatively depending on patient-related and radiographic factors. Displaced fractures should be reduced in the acute setting to better align the fracture fragments and a splint applied to hold the fracture in this position. Fractures that are acceptably reduced may be treated conservatively with casting and close radiographic follow-up to ensure maintained alignment. In this video, we describe our technique for closed reduction of distal radius fractures and review important factors that guide treatment., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)