Efficacy and safety of once-weekly semaglutide 2·4 mg versus placebo in people with obesity and prediabetes (STEP 10): a randomised, double-blind, placebo-controlled, multicentre phase 3 trial.

BACKGROUND: There are currently limited data regarding the effect of semaglutide 2·4 mg in individuals with obesity and prediabetes in clinical trials. We aimed to assess the efficacy and safety of semaglutide 2·4 mg for weight management and glycaemic control in participants with obesity and prediabetes. METHODS: STEP 10 was a randomised, double-blind, parallel-group, phase 3 trial done across 30 trial sites in Canada, Denmark, Finland, Spain, and the UK and included participants aged 18 years or older with a BMI of 30 kg/m2 or higher and prediabetes according to UK National Institute for Health and Care Excellence criteria (defined as having at least one of the following at screening: HbA1c of 6·0-6·4% [42-47 mmol/mol] or fasting plasma glucose [FPG] of 5·5-6·9 mmol/L). Participants were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2·4 mg or placebo with diet and physical activity counselling for 52 weeks, followed by a 28-week off-treatment period. Primary endpoints were percentage change in bodyweight and proportion of participants reverting to normoglycaemia (HbA1c <6·0% [<42 mmol/mol] and FPG <5·5 mmol/L) at week 52 (assessed in all randomly assigned participants by intention to treat). Selective safety data were collected for participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT05040971, and is complete. FINDINGS: Between Sept 16 and Dec 29, 2021, 138 participants were randomly assigned to semaglutide 2·4 mg and 69 to placebo. 147 (71%) were female and 60 (29%) were male; 183 (88%) were White. All randomly assigned participants received at least one dose of study drug. Baseline mean age was 53 years (SD 11), bodyweight 111·6 kg (22·2), BMI 40·1 kg/m2 (6·9), waist circumference 120·1 cm (14·7), HbA1c 5·9% (0·3; 41·3 mmol/mol [3·0]), and FPG 5·9 mmol/L (0·6). There was a significantly greater reduction in bodyweight with semaglutide 2·4 mg than with placebo at week 52 (-13·9% [SD 0·7] vs -2·7% [0·6]; estimated treatment difference -11·2% [95% CI -13·0 to -9·4]; p<0·0001). Greater proportions of participants reverted to normoglycaemia at week 52 with semaglutide 2·4 mg than with placebo (103 [81%] of 127 vs nine [14%] of 64; odds ratio 19·8 [95% CI 8·7 to 45·2]; p<0·0001). Serious adverse events occurred in 12 (9%) participants receiving semaglutide 2·4 mg versus six (9%) receiving placebo. Adverse events leading to treatment discontinuation occurred in eight (6%) participants in the semaglutide 2·4 mg group versus one (1%) participant in the placebo group. No new safety signals were reported. INTERPRETATION: Semaglutide 2·4 mg provided superior reduction in bodyweight and reversion to normoglycaemia versus placebo in participants with obesity and prediabetes. The safety and tolerability profile was consistent with previous studies and with the GLP-1 receptor agonist class. These findings support the potential use of semaglutide 2·4 mg as a treatment option for individuals with obesity and prediabetes to achieve reversion to normoglycaemia. FUNDING: Novo Nordisk. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Navigating the Aftermath: A Comprehensive Scoping Review on Follow-up Strategies After Kidney-sparing Surgery for Upper Tract Urothelial Carcinoma.

Background and objective: Upper tract urothelial carcinoma (UTUC) can be managed efficiently and safely through kidney-sparing surgery (KSS) in selected patient groups. However, the most effective and efficient postoperative surveillance strategy remains undetermined. We aimed to provide a comprehensive synopsis of the follow-up strategies and survival outcomes in patients diagnosed with UTUC treated by KSS. Methods: Following the systematic methodology outlined in the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews, we conducted searches in four databases (MEDLINE [Ovid], Embase [Ovid], Cochrane Library, and Web of Science) up until December 11, 2023. Key findings and limitations: A total of 3121 articles underwent screening, of which 19 were selected for inclusion in this review. The follow-up schedules after KSS exhibited considerable variability among the included studies. Diagnostic modalities employed consisted of computed tomography urography (present in 84% of protocols), X urography (21%), ultrasound (21%), thoracic imaging (26%), voided urine cytology (89%), selective upper tract cytology (5.3%), cystoscopy (84%), and ureterorenoscopy (53%) at varying frequencies. At 5 yr of follow-up, the reported recurrence-free survival rate ranged from 30% to 86%, overall survival was 50-92%, and metastasis-free survival was 77-90%. Conclusions and clinical implications: This review unveils significant heterogeneity in clinical practices and survival outcomes, indicating disparities between real-world approaches and guideline recommendations. The lack of consensus on follow-up schemes is evident, emphasising the necessity for future initiatives aimed at developing a comprehensive protocol. Patient summary: This review shows significant heterogeneity in follow-up strategies after kidney-sparing surgery for upper tract urothelial carcinoma. A lack of evidence contributes to discrepancies between guidelines and real-world approaches. Thus, future endeavours should aim at establishing a comprehensive protocol.

Decreasing Intraoperative Skin Damage in Prone-Position Surgeries.

OBJECTIVE: To determine if subepidermal moisture (SEM) measures help detect and prevent intraoperative acquired pressure injuries (IAPIs) for prone-position surgery. METHODS: In this clinical trial of patients (n = 39 preintervention, n = 48 intervention, 100 historical control) undergoing prone-position surgery, researchers examined the use of multidimensionally flexible silicone foam (MFSF) dressings applied preoperatively to patients' face, chest, and iliac crests. Visual skin assessments and SEM measures were obtained preoperatively, postoperatively, and daily for up to 5 days or until discharge. Electronic health record review included demographic, medical, and surgery data. RESULTS: Of the 187 total participants, 76 (41%) were women. Participants' mean age was 61.0 ± 15.0 years, and 9.6% were Hispanic (n = 18), 9.6% were Asian (n = 18), 6.9% were Black or African American (n = 13), and 73.8% were White (n = 138). Participants had a mean Scott-Triggers IAPI risk score of 1.5 ± 1.1. Among those with no erythema preoperatively, fewer intervention participants exhibited postoperative erythema on their face and chest than did preintervention participants. Further, fewer intervention participants had SEM-defined IAPIs at all locations in comparison with preintervention participants. The MFSF dressings overcame IAPI risk factors of surgery length, skin tone, and body mass index with fewer IAPIs in intervention participants. CONCLUSIONS: Patients undergoing prone-position surgeries developed fewer IAPIs, and SEM measures indicated no damage when MFSF dressings were applied to sites preoperatively. The SEM measures detected more damage than visual assessment.

A rapid review of motives and barriers for living substance of human origin donation and an extended typology.

Our objective is to review motives and barriers for non-reproductive, living substance of human origin (SoHO) donation, and to extend existing typologies beyond blood. The expansion of SoHO collection is currently unmatched by increased living donors. Thus, there is a critical need to understand how to effectively recruit and retain donors to ensure a sustainable supply of SoHO. We undertook a rapid review and narrative synthesis of published, peer-reviewed literature reporting on motives and/or barriers for living SoHO donation (whole-blood, blood products [2009-2023], bone marrow/stem cells, cord blood, organ, human breast milk, intestinal microbiota [2000-2023]). Results were interpreted through directed qualitative content analysis using an extended typology of motives/barriers largely drawn from blood donation research, and subsequently refined based on results to be inclusive of other SoHO. 234 articles with 237 studies met review criteria. Most were quantitative (74.3%), conducted in Western countries (63.8%), focused on blood donation (64.2%), reported motives and barriers (51.9%) and did not examine differences by donor characteristics or history (74%). We present a revised typology inclusive of motives/barriers for donation of substances beyond blood. This shows while broader motives and barriers are shared across substances donated, there are critical differences at the subcategory level that may account for heterogeneity in results of prior interventions. The nuances in how broad categories of motives and barriers manifest across different SoHO are critical for blood collection agencies to consider as they attempt to expand collection of products beyond whole-blood, plasma, and platelets. WHAT IS KNOWN ABOUT THE TOPIC?: Blood collection agencies (BCAs) continue to expand SoHO product collection beyond whole-blood, plasma, and platelets. The demand for SoHO is currently unmatched by increased living donors. The need to understand how to recruit new and retain existing living donors to ensure a sustainable supply of SoHO remains critical. However, there is no available synthesis of the factors, such as motives/facilitators and barriers/deterrents, to inform our understanding. WHAT IS NEW?: Comprehensively reviewed evidence for motives and barriers of willing/actual donors and nondonors across all types of non-reproductive living SoHO donation. Explored variations in motives and barriers based on substance, donor history and demographic differences (gender, age, ethnicity or culture). Extended typology of motives and barriers inclusive of all non-reproductive living SoHO, beyond solely whole-blood and blood products. Identified that while there are commonalities in the overarching motive and barrier categories across substances (e.g., prosocial motivation, low self-efficacy), within these broader constructs there are differences at the subcategory level (e.g., low-self efficacy was about eligibility, lifestyle barriers, or lack/loss of financial or material resources depending on the substance donated) that are crucial for development of future interventions and for BCAs to consider as they expand SoHO product collection. Highlighted the continued focus on motives and barriers for whole-blood and blood product donation to the exclusion of other, particularly newer, SoHO; lack of qualitative work for newer SoHO; and lack of consideration of differences based on donor characteristics (especially ethnicity/culture) and donor history, which limits our understanding. WHAT ARE THE KEY QUESTIONS FOR FUTURE WORK ON THE TOPIC?: What are the motives and barriers (in both qualitative and quantitative studies) for donation of newer SoHO such as stem cells, cord blood, human milk, and intestinal microbiota? Are there differences in motives and barriers within and across SoHO that are informed by individual and contextual-level factors? How can we develop interventions that respond to the nuances of motives and barriers present across different forms of SoHO that are effective in encouraging new and maintaining continuing donors?

Protocol for the development and validation of a clinical measurement tool for fear of disease progression and recurrence in cardiac patients.

Introduction: One in two cardiac patients fear having another heart event or their heart condition getting worse. Research in other chronic illnesses demonstrates that screening for fear of progression and recurrence is vital for adequately addressing such concerns in clinical care. The current project aims to develop and validate a measure for fear of progression and recurrence in cardiac patients. Methods: The Fear of Cardiac Recurrence and Progression Scale (FCRP) will be developed through a multistep process. An initial item pool will be generated through a review of the literature and existing measures and consultation with and feedback from key informants. The item pool will be tested in a sample of over 250 adults who have ever had an acute coronary event, undergone cardiac surgery, or a chronic cardiac condition. Exploratory factor analysis will be used to identify the underlying factors, and Rasch analysis will be used to reduce the number of items. A short form version of the FCRP will be developed for use as a brief screening tool, informed by clinical relevance and Rasch psychometric indices. Discussion: While many cardiac patients experience fears related to the progression or recurrence of their illness, there remains the need for a validated tool with which these concerns can be identified and measured. It is expected that the design and validation of the FCRP will aid identification of cardiac patients suffering from clinically significant levels of fear of progression and recurrence and facilitate the design of tailored psychological interventions to target these fears.

A rapid review of strategies to manage low iron levels in adults donating whole-blood: A focus on donor behaviour.

In recognition of the impact of whole-blood donation on body iron stores, there has been an increased focus assessing the efficacy of strategies to minimise the risk of iron deficiency (ID). Whilst donor behaviour is an important determinant of success, this literature is yet to be fully synthesised to help guide blood collection agencies when implementing these strategies into routine practice. This rapid review identifies strategies for management of low iron, how they have been communicated to donors, donor compliance with advice, donor use of external health services and their effect on donor retention. Web of Science, Medline, CINAHL and Wiley online library databases were searched from 2012 to November 2023, with 29 studies meeting inclusion criteria. Five iron management strategies were identified: oral iron supplementation (IS), education, dietary advice, lengthening inter-donation interval and switching donation type. Most studies (n = 16) focused on IS, with only four reporting how they communicated this to donors. Donor use of IS was high in controlled research environments but has not been evaluated when implemented into routine practice. None of the four studies on dietary advice included findings on donor acceptability. The proportion of donors consulting their doctor about a low iron result or their risk of ID was found to be suboptimal. However, in general, the identified strategies and communications had a positive effect on donor retention. More evidence is needed on how to increase donor knowledge and awareness of donation-related risk of ID as well as to identify how to effectively communicate strategies to donors to ensure optimal acceptability and use.

Bariatric and general surgical procedures in obese patients with a history of venous thromboembolism and concurrent anticoagulation therapy.

OBJECTIVE: The objective of this study was to examine the use and outcomes of perioperative anticoagulation (AC) in obese patients with a known history of venous thromboembolism event (VTE). METHOD: A retrospective review of a prospective database for patients with a VTE history undergoing bariatric and general surgery at a single center (1/2008-12/2017) was performed. Factors assessed included demographics, surgical details, and outcomes. RESULTS: Sixty-five patients underwent 76 procedures: 46 females (71%); mean age 51 years (range 26-73), mean weight 284 pounds (range 110-558), mean body mass index 45 (range 19-87). Comorbidities include hypertension (60%), gastroesophageal reflux disease (54%), osteoarthritis (49%), obstructive sleep apnea (45%), and diabetes (37%). Operations: 22 general surgeries (29%), 20 sleeve gastrectomies (26%), 12 revisions/conversions (16%), 12 Roux-en-Y gastric bypasses (16%), and 10 gastric bands (13%). Modalities: 67% laparoscopic, 28% robotic, and 5% open. Twenty-two patients (34%) had a pre-operative inferior vena cava filter placed with no complications. The mean length of stay was 4.4 days (range 1-31). Complications: seven 30-day readmissions (9%), one 30-day reoperation (1%), and two 90-day VTEs (3%). Thirty-day readmissions: four for inability to tolerate PO, two for small bowel obstruction, and one for symptomatic anastomotic ulcer. CONCLUSIONS: In our patients, post-operative AC could be started without an increased risk of bleeding in patients with a history of VTE undergoing bariatric surgery.

OBJETIVO: Examinar el uso y los resultados de la anticoagulación perioperatoria en pacientes bariátricos con antecedentes de tromboembolia venosa (TEV). MÉTODO: Revisión retrospectiva (base de datos prospectiva) de pacientes sometidos a cirugía general y bariátrica (1/2008-12/2017). Se evaluaron datos demográficos, detalles quirúrgicos y resultados. RESULTADOS: Sesenta y cinco pacientes se sometieron a 76 procedimientos: 46 mujeres (71%), edad media 51 años (rango: 26-73), peso medio 284 libras (rango: 110-558), índice de masa corporal medio 45 (rango: 19-87). Comorbilidad: hipertensión (60%), enfermedad por reflujo gastroesofágico (54%), osteoartritis (49%), apnea obstructiva del sueño (45%), diabetes (37%). Operaciones: 22 cirugía general (29%), 20 gastrectomías en manga (26%), 12 revisiones/conversiones (16%), 12 Y-de-Roux (16%), 10 bandas gástricas (13%). Modalidades: 67% laparoscópica, 28% robótica, 5% abierta. A 22 pacientes (34%) se les colocó un filtro de vena cava inferior preoperatorio sin complicaciones. La estancia media fue de 4.4 días (rango: 1-31). Complicaciones: 7 reingresos a los 30 días (9%), 1 reoperación a los 30 días (1%), 2 TEV a los 90 días (3%). Reingresos a los 30 días: 4 por incapacidad para tolerar la vía oral, 2 obstrucciones de intestino delgado y 1 úlcera anastomótica sintomática. CONCLUSIONES: En nuestros casos, la anticoagulación posoperatoria pudo iniciarse sin aumento del riesgo de sangrado en pacientes con antecedentes de TVE sometidos a cirugía bariátrica.

Streamlining Research Metrics Compilation Reports: An Automated Approach Using Scopus and Clarivate APIs.

This article examines the development and implementation of a customized Python script utilizing the Elsevier Scopus and Clarivate Web of Science Journal Citation Reports Application Programming Interfaces (APIs). The aim was to streamline and expedite the labor-intensive process of collecting research metrics, which were traditionally compiled manually by librarians at the University of Miami Miller School of Medicine Louis Calder Memorial Library. The script significantly reduces the time and effort required to generate comprehensive reports on research productivity, thereby enabling more efficient resource allocation and aiding in faculty evaluations.

The extracellular serine protease from Staphylococcus epidermidis elicits a type 2-biased immune response in atopic dermatitis patients.

Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with skin barrier defects and a misdirected type 2 immune response against harmless antigens. The skin microbiome in AD is characterized by a reduction in microbial diversity with a dominance of staphylococci, including Staphylococcus epidermidis (S. epidermidis). Objective: To assess whether S. epidermidis antigens play a role in AD, we screened for candidate allergens and studied the T cell and humoral immune response against the extracellular serine protease (Esp). Methods: To identify candidate allergens, we analyzed the binding of human serum IgG4, as a surrogate of IgE, to S. epidermidis extracellular proteins using 2-dimensional immunoblotting and mass spectrometry. We then measured serum IgE and IgG1 binding to recombinant Esp by ELISA in healthy and AD individuals. We also stimulated T cells from AD patients and control subjects with Esp and measured the secreted cytokines. Finally, we analyzed the proteolytic activity of Esp against IL-33 and determined the cleavage sites by mass spectrometry. Results: We identified Esp as the dominant candidate allergen of S. epidermidis. Esp-specific IgE was present in human serum; AD patients had higher concentrations than controls. T cells reacting to Esp were detectable in both AD patients and healthy controls. The T cell response in healthy adults was characterized by IL-17, IL-22, IFN-γ, and IL-10, whereas the AD patients' T cells lacked IL-17 production and released only low amounts of IL-22, IFN-γ, and IL-10. In contrast, Th2 cytokine release was higher in T cells from AD patients than from healthy controls. Mature Esp cleaved and activated the alarmin IL-33. Conclusion: The extracellular serine protease Esp of S. epidermidis can activate IL-33. As an antigen, Esp elicits a type 2-biased antibody and T cell response in AD patients. This suggests that S. epidermidis can aggravate AD through the allergenic properties of Esp.

Pharmacotherapy for older people with obesity.

Rates of obesity continue to rise, including in older adults. Use of medication for obesity in the elderly has been considered controversial, due to concerns around potential progression of age-related sarcopenia and a general lack of evidence for its use in this age group. Within this review, we describe the general considerations when prescribing obesity pharmacotherapy for older adults living with obesity. We evaluate in detail the anti-obesity medications currently licenced in Europe, with emphasis on the available efficacy, safety and cardiovascular outcome data gathered from study of older people. Finally, we discuss future directions and avenues of research.

Clinical effectiveness and cost-effectiveness of Structured Psychological Support for people with probable personality disorder in mental health services in England: study protocol for a randomised controlled trial.

INTRODUCTION: Evidence-based psychological treatments for people with personality disorder usually involve attending group-based sessions over many months. Low-intensity psychological interventions of less than 6 months duration have been developed, but their clinical effectiveness and cost-effectiveness are unclear. METHODS AND ANALYSIS: This is a multicentre, randomised, parallel-group, researcher-masked, superiority trial. Study participants will be aged 18 and over, have probable personality disorder and be treated by mental health staff in seven centres in England. We will exclude people who are: unwilling or unable to provide written informed consent, have a coexisting organic or psychotic mental disorder, or are already receiving psychological treatment for personality disorder or on a waiting list for such treatment. In the intervention group, participants will be offered up to 10 individual sessions of Structured Psychological Support. In the control group, participants will be offered treatment as usual plus a single session of personalised crisis planning. The primary outcome is social functioning measured over 12 months using total score on the Work and Social Adjustment Scale (WSAS). Secondary outcomes include mental health, suicidal behaviour, health-related quality of life, patient-rated global improvement and satisfaction, and resource use and costs. The primary analysis will compare WSAS scores across the 12-month period using a general linear mixed model adjusting for baseline scores, allocation group and study centre on an intention-to-treat basis. In a parallel process evaluation, we will analyse qualitative data from interviews with study participants, clinical staff and researchers to examine mechanisms of impact and contextual factors. ETHICS AND DISSEMINATION: The study complies with the Helsinki Declaration II and is approved by the London-Bromley Research Ethics Committee (IRAS ID 315951). Study findings will be published in an open access peer-reviewed journal; and disseminated at national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN13918289.

Clinical Implementation of DIGEST as an Evidence-Based Practice Tool for Videofluoroscopy in Oncology: A Six-Year Single Institution Implementation Evaluation.

Clinical implementation of evidence-based practice (EBP) tools is a healthcare priority. The Dynamic Grade of Swallowing Toxicity (DIGEST) is an EBP tool developed in 2016 for videofluoroscopy in head and neck (H&N) oncology with clinical implementation as a goal. We sought to examine: (1) feasibility of clinical implementation of DIGEST in a national comprehensive cancer center, and (2) fidelity of DIGEST adoption in real-world practice. A retrospective implementation evaluation was conducted in accordance with the STARI framework. Electronic health record (EHR) databases were queried for all consecutive modified barium swallow (MBS) studies conducted at MD Anderson Cancer Center from 2016 to 2021. Implementation outcomes included: feasibility as measured by DIGEST reporting in EHR (as a marker of clinical use) and fidelity as measured by accuracy of DIGEST reporting relative to the decision-tree logic (penetration-aspiration scale [PAS], residue, and Safety [S] and Efficiency [E] grades). Contextual factors examined included year, setting, cancer type, MBS indication, and provider. 13,055 MBS were conducted by 29 providers in 7,842 unique patients across the lifespan in diverse oncology populations (69% M; age 1-96 years; 58% H&N cancer; 10% inpatient, 90% outpatient). DIGEST was reported in 12,137/13,088 exams over the 6-year implementation period representing 93% (95% CI: 93-94%) adoption in all exams and 99% (95% CI: 98-99%) of exams excluding the total laryngectomy population (n = 730). DIGEST reporting varied modestly by year, cancer type, and setting/provider (> 91% in all subgroups, p < 0.001). Accuracy of DIGEST reporting was high for overall DIGEST (incorrect SE profile 1.6%, 200/12,137), DIGEST-safety (incorrect PAS 0.4% 51/12,137) and DIGEST-efficiency (incorrect residue 1.2%, 148/12,137). Clinical implementation of DIGEST was feasible with high fidelity in a busy oncology practice across a large number of providers. Adoption of the tool across the lifespan in diverse cancer diagnoses may motivate validation beyond H&N oncology.

'Yeah, this is my donation': An application of psychological ownership in blood donation.

To meet the priority healthcare needs of any population there must be a consistently available blood supply donated by willing donors. Due to this universal need for blood, retaining blood donors remains an ongoing challenge for blood services internationally. Encouraging psychological ownership, or the feeling of ownership one experiences over a possession, provides a potential novel solution to donor retention. This study, based on semi-structured interviews with blood donors, investigates how donors perceive and develop psychological ownership in the context of blood donation. Interviews were conducted in Australia with 20 current blood donors (10 men, 10 women; Mage = 41.95). Through thematic analysis, six themes were identified based primarily on the theoretical framework of psychological ownership. This research offers a novel perspective on donor retention, suggesting that donors' ownership over their individual donation practices, and not the blood service, may contribute to maintaining a stable blood supply.

Healthcare cost expenditure for robotic versus laparoscopic liver resection: a bottom-up economic evaluation.

BACKGROUND: Minimally invasive liver surgery (MILS) is increasingly performed via the robot-assisted approach but may be associated with increased costs. This study is a post-hoc comparison of healthcare cost expenditure for robotic liver resection (RLR) and laparoscopic liver resection (LLR) in a high-volume center. METHODS: In-hospital and 30-day postoperative healthcare costs were calculated per patient in a retrospective series (October 2015-December 2022). RESULTS: Overall, 298 patients were included (143 RLR and 155 LLR). Benefits of RLR were lower conversion rate (2.8% vs 12.3%, p = 0.002), shorter operating time (167 min vs 198 min, p = 0.044), and less blood loss (50 mL vs 200 mL, p < 0.001). Total per-procedure costs of RLR (€10260) and LLR (€9931) were not significantly different (mean difference €329 [95% bootstrapped confidence interval (BCI) €-1179-€2120]). Lower costs with RLR due to shorter surgical and operating room time were offset by higher disposable instrumentation costs resulting in comparable intraoperative costs (€5559 vs €5247, mean difference €312 [95% BCI €-25-€648]). Postoperative costs were similar for RLR (€4701) and LLR (€4684), mean difference €17 [95% BCI €-1357-€1727]. When also considering purchase and maintenance costs, RLR resulted in higher total per-procedure costs. DISCUSSION: In a high-volume center, RLR can have similar per-procedure cost expenditure as LLR when disregarding capital investment.

Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer.

BACKGROUND: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. METHODS: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated. RESULTS: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year's testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths. CONCLUSIONS: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.

Mercury Concentrations in Two Populations of the most Endangered Dolphin (Pontoporia blainvillei) from the Southwestern Atlantic Ocean.

Mercury contamination has been aggravated by emerging environmental issues, such as climate change. Top predators present concerning Hg concentrations once this metal bioaccumulates and biomagnifies. This study evaluated total mercury (THg) concentrations in tissues of 43 franciscanas (Pontoporia blainvillei) from two populations: the Franciscana Management Area (FMA) IIb and FMA IIIa. Animals from FMA IIIa showed mean concentration 5-times and 2.5-times higher in the liver and kidney (4.73 ± 6.84 and 0.52 ± 0.51 µg.g-1, w.w., respectively) than individuals from FMA IIb (0.89 ± 1.04 and 0.22 ± 0.15 µg.g-1, w.w., respectively). This might be due to: (I) individuals sampled from FMA IIIa being larger and older, and/or (II) the area near FMA IIIa presents environmental features leading to higher THg availability. Coastal contamination can affect franciscanas' health and population maintenance at different levels depending on their life history and, therefore, it should be considered to guide specific conservation actions.

Healthy tissue metabolism assessed by [18F]FDG PET/CT as a marker of prognosis and adverse events in advanced Hodgkin lymphoma patients.

The aim of the study was to assess healthy tissue metabolism (HTM) using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) during chemotherapy in Hodgkin lymphoma (HL) and the association of HTM with baseline metabolic tumour volume (MTV), haematological parameters, adverse events (AEs), early response and progression-free survival (PFS). We retrospectively identified 200 patients with advanced HL from the RATHL trial with [18F]FDG-PET/CT before (PET0) and following 2 cycles of chemotherapy (PET2). [18F]FDG-uptake was measured in bone marrow (BM), spleen, liver and mediastinal blood pool (MBP). Deauville score (DS) 1-3 was used to classify responders and DS 4-5, non-responders. [18F]FDG-uptake decreased significantly in BM and spleen and increased in liver and MBP at PET2 (all p < 0.0001), but was not associated with MTV. Higher BM uptake at PET0 was associated with lower baseline haemoglobin and higher absolute neutrophil counts, platelets, and white blood cells. High BM, spleen, and liver uptake at PET0 was associated with neutropenia after cycles 1-2. BM uptake at PET0 was associated with treatment failure at PET2 and non-responders with higher BM uptake at PET2 had significantly inferior PFS (p = 0.023; hazard ratio = 2.31). Based on these results, we concluded that the change in HTM during chemotherapy was most likely a direct impact of chemotherapy rather than a change in MTV. BM uptake has prognostic value in HL.

Genetic relationships between behavioral traits and feed efficiency traits in lactating Holstein cows.

The evaluation of dairy cow feed efficiency using residual feed intake accounts for known energy sinks. However, behavioral traits may also contribute to the variation in feed efficiency. Our objective was to estimate the heritability and repeatability of behavioral traits and their genetic correlations with feed efficiency and its components in lactating Holstein cows. The first data set consisted of 36,075 daily rumination and lying time records collected using a SMARTBOW ear tag accelerometer (Zoetis, Parsippany, NJ) and 6,371 weekly feed efficiency records of 728 cows from the University of Wisconsin-Madison. The second data set consisted of 59,155 daily activity records, measured as number of steps, recorded by pedometers (AfiAct; S.A.E. Afikim, Kibbutz Afikim, Israel), and 8,626 weekly feed efficiency records of 635 cows from the University of Florida. Feed efficiency and its components included dry matter intake, change in body weight, metabolic body weight, secreted milk energy, and residual feed intake. The statistical models included the fixed effect of cohort, lactation number, and days in milk, and the random effects of animal and permanent environment. Heritability estimates for behavioral traits using daily records were 0.19 ± 0.06 for rumination and activity, and 0.37 ± 0.07 for lying time. Repeatability estimates for behavioral traits using daily data ranged from 0.56 ± 0.02 for activity to 0.62 ± 0.01 for lying time. Both heritability and repeatability estimates were larger when weekly records instead of daily records were used. Rumination and activity had positive genetic correlations with residual feed intake (0.40 ± 0.19 and 0.31 ± 0.22, respectively) while lying time had a negative genetic correlation with this residual feed intake (-0.27 ± 0.11). These results indicate that more efficient cows tend to spend more time lying and less time active. Additionally, less efficient cows tend to eat more and therefore also tend to ruminate longer. Overall, sensor-based behavioral traits are heritable and genetically correlated with feed efficiency and its components and, therefore, they could be used as indicators to identify feed efficient cows within the herd.