An aged immune system drives senescence and ageing of solid organs.

Ageing of the immune system, or immunosenescence, contributes to the morbidity and mortality of the elderly1,2. To define the contribution of immune system ageing to organism ageing, here we selectively deleted Ercc1, which encodes a crucial DNA repair protein3,4, in mouse haematopoietic cells to increase the burden of endogenous DNA damage and thereby senescence5-7 in the immune system only. We show that Vav-iCre+/-;Ercc1-/fl mice were healthy into adulthood, then displayed premature onset of immunosenescence characterized by attrition and senescence of specific immune cell populations and impaired immune function, similar to changes that occur during ageing in wild-type mice8-10. Notably, non-lymphoid organs also showed increased senescence and damage, which suggests that senescent, aged immune cells can promote systemic ageing. The transplantation of splenocytes from Vav-iCre+/-;Ercc1-/fl or aged wild-type mice into young mice induced senescence in trans, whereas the transplantation of young immune cells attenuated senescence. The treatment of Vav-iCre+/-;Ercc1-/fl mice with rapamycin reduced markers of senescence in immune cells and improved immune function11,12. These data demonstrate that an aged, senescent immune system has a causal role in driving systemic ageing and therefore represents a key therapeutic target to extend healthy ageing.

The Epigenetic Reader, Bromodomain Containing 2, Mediates Cholangiocyte Senescence via Interaction With ETS Proto-Oncogene 1.

BACKGROUND & AIMS: We reported that cholangiocyte senescence, regulated by the transcription factor ETS proto-oncogene 1 (ETS1), is a pathogenic feature of primary sclerosing cholangitis (PSC). Furthermore, histone 3 lysine 27 is acetylated at senescence-associated loci. The epigenetic readers, bromodomain and extra-terminal domain (BET) proteins, bind acetylated histones, recruit transcription factors, and drive gene expression. Thus, we tested the hypothesis that BET proteins interact with ETS1 to drive gene expression and cholangiocyte senescence. METHODS: We performed immunofluorescence for BET proteins (BRD2 and 4) in liver tissue from liver tissue from PSC patients and a mouse PSC model. Using normal human cholangiocytes (NHCs), NHCs experimentally induced to senescence (NHCsen), and PSC patient-derived cholangiocytes (PSCDCs), we assessed senescence, fibroinflammatory secretome, and apoptosis after BET inhibition or RNA interference depletion. We assessed BET interaction with ETS1 in NHCsen and tissues from PSC patient, and the effects of BET inhibitors on liver fibrosis, senescence, and inflammatory gene expression in mouse models. RESULTS: Tissue from patients with PSC and a mouse PSC model exhibited increased cholangiocyte BRD2 and 4 protein (∼5×) compared with controls without disease. NHCsen exhibited increased BRD2 and 4 (∼2×), whereas PSCDCs exhibited increased BRD2 protein (∼2×) relative to NHC. BET inhibition in NHCsen and PSCDCs reduced senescence markers and inhibited the fibroinflammatory secretome. ETS1 interacted with BRD2 in NHCsen, and BRD2 depletion diminished NHCsen p21 expression. BET inhibitors reduced senescence, fibroinflammatory gene expression, and fibrosis in the 3,5-diethoxycarbonyl-1,4-dihydrocollidine-fed and Mdr2-/- mouse models. CONCLUSION: Our data suggest that BRD2 is an essential mediator of the senescent cholangiocyte phenotype and is a potential therapeutic target for patients with PSC.

Trends and Determinants of Location of Death Due to Colorectal Cancer in the United States : A Nationwide Study.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States (US); however, there are limited data on location of death in patients who die from CRC. We examined the trends in location of death and determinants in patients dying from CRC in the US. METHODS: We utilized the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database to extract nationwide data on underlying cause of death as CRC. A multinomial logistic regression was performed to assess associations between clinico-sociodemographic characteristics and location of death. RESULTS: There were 850,750 deaths due to CRC from 2003 to 2019. There was a gradual decrease in deaths in hospital, nursing home, or outpatient facility/emergency department over time and an increase in deaths at home and in hospice. Relative to White decedents, Black, Asian, and American Indian/Alaska Native decedents were less likely to die at home and in hospice compared with hospitals. Individuals with lower educational status also had a lower risk of dying at home or in hospice compared with in hospitals. CONCLUSIONS: The gradual shift in location of death of patients who die of CRC from institutionalized settings to home and hospice is a promising trend and reflects the prioritization of patient goals for end-of-life care by healthcare providers. However, there are existing sociodemographic disparities in access to deaths at home and in hospice, which emphasizes the need for policy interventions to reduce health inequity in end-of-life care for CRC.

Geriatric Assessment in Colorectal Surgery: A Systematic Review.

INTRODUCTION: The prevalence of colorectal surgery among older adults is expected to rise due to the aging population. Geriatric conditions (e.g., frailty) are risk factors for poor surgical outcomes. The goal of this systematic review is to examine how current literature describes geriatric assessment interventions in colorectal surgery and associated outcomes. METHODS: Systematic searches of Ovid MEDLINE, Cochrane Library, CINAHL, Embase, and Web of Science were completed. Review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered in PROSPERO, the international prospective register of systematic reviews in health and social care. All cohort studies and randomized trials of adult colorectal surgery patients where geriatric assessment was performed were included. Geriatric assessment with/without management interventions were identified and described. RESULTS: Seven-hundred ninety-three studies were identified. Duplicates (197) were removed. An additional 525 were excluded after title/abstract review. After full-text review, 20 studies met the criteria. Reference list review increased final total to 25 studies. All 25 studies were cohort studies. No randomized clinical trials were identified. Heterogeneous assessments were organized into geriatrics domains (mind, mobility, medications, matters most, and multi-complexity). Incomplete evaluations across geriatric domains were performed with few studies describing the use of assessments to impact management decisions. CONCLUSIONS: There are no randomized trials assessing the impact of geriatric assessment to tailor management strategies and improve outcomes in colorectal surgery. Few studies performed assessments to evaluate the geriatric domain matters most. These findings represent a gap in evidence for the efficacy of geriatric assessment and management strategies in colorectal surgical care.

Incidence of Secondary Cancers After Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

INTRODUCTION: Whether neoadjuvant chemoradiation for locally advanced rectal cancer (LARC) induces secondary cancers is controversial. This retrospective cohort study describes the incidence of secondary cancers in LARC patients. METHODS: We compared 364 LARC patients who received conventional (50.4 Gy) or short course neoadjuvant radiation (25 Gy x 5 fractions) followed by resection to 142 patients with surgically resected rectal cancer who did not receive radiation at a single institution from 2004 to 2018. Secondary cancer was defined as any nonmetastatic noncolorectal malignancy diagnosed via biopsy or definitive imaging criteria at least 6 mo after completion of neoadjuvant therapy or after resection in the comparison group. RESULTS: Among the neoadjuvant radiation group (364 patients, 40% female, age 61 ± 13 y), 32 patients developed 34 (9.3%) secondary cancers. Three cases involved a pelvic organ. Among the comparison group (142 patients, 39% female, age 64 ± 15 y), 15 patients (10.6%) developed a secondary cancer. Five cases involved pelvic organs. Secondary cancer incidence did not differ between groups. Latency period to secondary cancer diagnosis was 6.7 ± 4.3 y. Patients who received radiation underwent longer median follow-up (6.8 versus 4.5 y, P < 0.01) and were significantly less likely to develop a pelvic organ cancer (odds ratio 0.18; 95% confidence interval, 0.04-0.83; P = 0.02). No genetic mutations or cancer syndromes were identified among patients with secondary cancers. CONCLUSIONS: Neoadjuvant chemoradiation is not associated with increased secondary cancer risk in LARC patients and may have a local protective effect on pelvic organs, especially prostate. Ongoing follow-up is critical to continue risk assessment.

Mpox Illness Narratives: Stigmatising Care and Recovery During and After an Emergency Outbreak.

In May 2022, a global outbreak of mpox (formerly monkeypox virus) affected thousands of mainly gay and bisexual men. Mpox is usually a time-limited illness that can involve fever, pain, and skin lesions, but may require hospitalisation. There is scant research into the firsthand experiences of people affected by mpox, including experiences of symptoms, healthcare, and recovery. This study considers the different illness narratives of people who experienced mpox in Australia in 2022. In-depth interviews and 6-month follow-up interviews were conducted with 16 people, including 13 people diagnosed with mpox and three close contacts. All participants were cisgender gay or bisexual men living in Australia. Participants' accounts described minor to severe periods of sickness, negative and stigmatising experiences engaging with healthcare, and some participants experienced long-term effects on their sexual well-being and complications from mpox. The emergency outbreak context meant that mpox was highly distressing, making it difficult to manage and producing varying forms of disruption to everyday life. Mpox was narrated as disruptive in different ways: as a minor interruption to holiday plans, a prolonged period of poor health, or a biographically disruptive event prompting a re-evaluation of sexual values and health. This analysis demonstrates that an unfamiliar emergent disease outbreak related to sexual practices and sociality can reconfigure personal life and sexual well-being, suggesting a need to focus on providing quality patient care in outbreaks of mpox and other infectious diseases.

Perceptions of Mobile Health Technology in Elective Surgery: A Qualitative Study of North American Surgeons.

OBJECTIVES: To explore the surgeon-perceived added value of mobile health technologies (mHealth), and determine facilitators of and barriers to implementing mHealth. BACKGROUND: Despite the growing popularity of mHealth and evidence of meaningful use of patient-generated health data in surgery, implementation remains limited. METHODS: This was an exploratory qualitative study following the Consolidated Criteria for Reporting Qualitative Research. Purposive sampling was used to identify surgeons across the United States and Canada. The Consolidated Framework for Implementation Research informed development of a semistructured interview guide. Video-based interviews were conducted (September-November 2020) and interview transcripts were thematically analyzed. RESULTS: Thirty surgeons from 8 specialties and 6 North American regions were interviewed. Surgeons identified opportunities to integrate mHealth data pre- operatively (eg, expectation-setting, decision-making) and during recovery (eg, remote monitoring, earlier detection of adverse events) among higher risk patients. Perceived advantages of mHealth data compared with surgical and patient-reported outcomes included easier data collection, higher interpretability and objectivity of mHealth data, and the potential to develop more patientcentered and functional measures of health. Surgeons identified a variety of implementation facilitators and barriers around surgeon- and patient buy-in, integration with electronic medical records, regulatory/reimbursement concerns, and personnel responsible for mHealth data. Surgeons described similar considerations regarding perceptions of mHealth among patients, including the potential to address or worsen existing disparities in surgical care. CONCLUSIONS: These findings have the potential to inform the effective and equitable implementation of mHealth for the purposes of supporting patients and surgical care teams throughout the delivery of surgical care.

Autophagy promotes hepatic cystogenesis in polycystic liver disease by depletion of cholangiocyte ciliogenic proteins.

BACKGROUNDS AND AIMS: Polycystic liver disease (PLD) is characterized by defective cholangiocyte cilia that regulate progressive growth of hepatic cysts. Because formation of primary cilia is influenced by autophagy through degradation of proteins involved in ciliogenesis, we hypothesized that ciliary defects in PLD cholangiocytes (PLDCs) originate from autophagy-mediated depletion of ciliogenic proteins ADP-ribosylation factor-like protein 3 (ARL3) and ADP-ribosylation factor-like protein 13B (ARL13B) and ARL-dependent mislocation of a ciliary-localized bile acid receptor, Takeda G-protein-coupled receptor 5 (TGR5), the activation of which enhances hepatic cystogenesis (HCG). The aims here were to determine whether: (1) ciliogenesis is impaired in PLDC, is associated with increased autophagy, and involves autophagy-mediated depletion of ARL3 and ARL13B; (2) depletion of ARL3 and ARL13B in PLDC cilia impacts ciliary localization of TGR5; and (3) pharmacological inhibition of autophagy re-establishes cholangiocyte cilia and ciliary localization of ARL3, ARL3B, and TGR5 and reduces HCG. APPROACH AND RESULTS: By using liver tissue from healthy persons and patients with PLD, in vitro and in vivo models of PLD, and in vitro models of ciliogenesis, we demonstrated that, in PLDCs: ciliogenesis is impaired; autophagy is enhanced; ARL3 and ARL13B are ubiquitinated by HDAC6, depleted in cilia, and present in autophagosomes; depletion of ARL3 and ARL13B impacts ciliary localization of TGR5; and pharmacological inhibition of autophagy with mefloquine and verteporfin re-establishes cholangiocyte cilia and ciliary localization of ARL3, ARL13B, and TGR5 and reduces HCG. CONCLUSIONS: The intersection between autophagy, defective cholangiocyte cilia, and enhanced HCG contributes to PLD progression and can be considered a target for therapeutic interventions.

Logics of control and self-management in narratives of people living with HIV, hepatitis C and hepatitis B.

In Australia, the response to HIV, hepatitis C and hepatitis B has largely been through the constructed category of 'blood borne viruses' which treats these viruses as an interconnected set of conditions with respect to their mode of transmission. In this paper, we explore how people understand their viral infection, and compare the logics underpinning these different understandings. In-depth interviews were conducted with 61 participants who were either living with a blood borne virus or were the family members of people living with them. Our analysis reveals that the viral infection was often described as 'just a condition that needs to be managed', albeit in potentially exhausting ways. This understanding hinged upon a biomedical logic in which viral invasion was seen as causing illness and in turn necessitating biomedical intervention. In contrast, some participants with hepatitis B presented their infection as a condition unintelligible through Western biomedical logics, defined instead by symptomology - in terms of 'liver disease', and/or 'liver inflammation'. This focus on symptomology calls into question the soundness of prevention and management responses to hepatitis B based in biomedical logics and reveals the extent to which living with a virus involves multiple, sometimes incompatible, cultural logics. The different logics underpinning HIV, hepatitis C and hepatitis B reveal shortcomings of framing these viruses together as a coherent single construct.

Is sex lost in translation? Linguistic and conceptual issues in the translation of sexual and reproductive health surveys.

Translated questionnaires are increasingly used in population health research. Nevertheless, translation is often not conducted with the same rigour as the process of survey development in the original language. This has serious limitations and may introduce bias in question relevance and meaning. This article describes and reflects on the process of translating a large and complex sexual and reproductive health survey from English into Simplified Chinese. We interrogated assumptions embedded in taken-for-granted translation practice to locate the sociocultural origins of these assumptions. We discuss how terminology and expression related to sexual and reproductive health may lose their conceptual or linguistic significance during translation in three different ways. Firstly, meanings can be lost in the negotiation of meanings associated with linguacultural and geographical variations of terminology. Secondly, meanings can be lost in the clash between everyday and professional sexual and reproductive health discourses. Thirdly, meanings can be lost due to the design of the source questionnaire and the intended mode of survey administration. We discuss ways to help overcome the unavoidable translation challenges that arise in the process of translating English sexual and reproductive health surveys for migrants from non-English speaking backgrounds.

Understanding the health care needs of transgender and gender diverse people engaging with rural Australian sexual health centres: a qualitative interview study.

BACKGROUND: Although there is a presumption that LGBTQ+ people living in rural Australia will have poorer health outcomes than those living in metropolitan areas, minimal research has focused specifically on the perspectives of transgender and gender diverse (henceforth referred to as 'trans') people living in these regions. The purpose of this study was to understand what health and wellbeing means to trans people in a regional or rural community and identify their health needs and experiences. METHODS: A total of 21 trans people were recruited through two regional sexual health centres (SHC) and interviewed between April and August 2021. Data were analysed via reflexive thematic analysis. This paper focuses on participants' accounts of health and wellbeing regarding gender affirmation, the experience of rural living, respectful holistic care, safety in rural communities, isolation, loneliness, and employment. RESULTS: The experience of living rurally can have both positive and negative impacts on the experiences of trans people. Participants reported experiences of stigma and discrimination, reduced employment opportunities and limited social interactions, which led to feelings of isolation and loneliness; however, they also reported high quality of care, particularly with the specific SHCs which supported this research. CONCLUSION: Living rurally can impact both positively and negatively on the health and wellbeing of trans peoples, and the experiences of living in this environment are diverse. Our findings challenge the perception that rural trans people experience only poor health outcomes and shows the difference that key health services such as SHCs can make in supporting trans health.

The freighted social histories of HIV and hepatitis C: exploring service providers' perspectives on stigma in the current epidemics.

A virus has a social history. In the case of the hepatitis C virus (HCV) and HIV, this history is one involving stigma and discrimination, advocacy and activism, and recent dramatic improvements in treatment. These social histories influence the experience of people who live with the viruses, and those who work with them. One aspect of this is the impact of social changes on the biographical disruption and integration brought about by illness. Healthcare practitioners who see significant improvements in the effectiveness of treatment for a condition over the course of their professional life will incorporate those changes into their own history and their relationship to that condition.This article is based on a study of the experiences of serodiscordance, or mixed infection status, in families living with HIV and two types of viral hepatitis, hepatitis B and hepatitis C. The article explores the perspectives of healthcare workers who work with people affected by these viruses, who were asked about their experiences in working with serodiscordance in families. Interviews revealed that changing social meanings given to bloodborne viruses, and changes to treatment over time, held a significant place in the accounts that service providers gave of their work. In asking them to describe their work with HIV and HCV, we were also asking about work that has been shaped by changing patterns and sources of stigma, and recently reshaped by changes in treatment and outcomes. While typically the experiences of patients and their families are used to investigate the social histories of diagnosis and stigma, the professional perspectives and life stories of the service providers who work with them are also revealing. We heard accounts in which histories as well as current regimes were prominent, illuminated further by insights from the sociology of health on narrative and biographical disruption.

Smartphone-based Assessment of Preoperative Decision Conflict and Postoperative Physical Activity Among Patients Undergoing Cancer Surgery: A Prospective Cohort Study.

OBJECTIVE: To determine the prevalence of clinically significant decision conflict (CSDC) among patients undergoing cancer surgery and associations with postoperative physical activity, as measured through smartphone accelerometer data. BACKGROUND: Patients with cancer face challenging treatment decisions, which may lead to CSDC. CSDC negatively affects patient-provider relationships, psychosocial functioning, and health-related quality of life; however, physical manifestations of CSDC remain poorly characterized. METHODS: Adult smartphone-owners undergoing surgery for breast, skin-soft-tissue, head-and-neck, or abdominal cancer (July 2017-2019) were approached. Patients downloaded the Beiwe application that delivered the Decision Conflict Scale (DCS) preoperatively and collected smartphone accelerometer data continuously from enrollment through 6 months postop-eratively. Restricted-cubic-spline regression, adjusting for a priori potential confounders (age, type of surgery, support status, and postoperative complications) was used to determine trends in postoperative daily physical activity among patients with and without CSDC (DCS score >25/100). RESULTS: Among 99 patients who downloaded the application, 85 completed the DCS (86% participation rate). Twenty-three (27%) reported CSDC. These patients were younger (mean age 48.3 years [standard deviation 14.2]-vs-55.0 [13.3], P = 0.047) and more frequently lived alone (22%-vs-6%, P = 0.042). There were no differences in preoperative physical activity (115.4 minutes [95%CI 90.9, 139.9]-vs-110.8 [95%CI 95.7, 126.0], P = 0.753). Adjusted postoperative physical activity was lower among patients reporting CSDC at 30 days (difference 33.1 minutes [95%CI 5.93,60.2], P = 0.017), 60 days 35.5 [95%CI 8.50, 62.5], P = 0.010 and 90 days 31.8 [95%CI 5.44, 58.1], P = 0.018 postoperatively. CONCLUSIONS: CSDC was prevalent among patients who underwent cancer surgery and associated with lower postoperatively daily physical activity. These data highlight the importance of addressing modifiable decisional needs of patients through enhanced shared decision-making.

Molecular Basis of Extramural Vascular Invasion (EMVI) in Colorectal Carcinoma.

BACKGROUND: Extramural vascular invasion (EMVI) is a known poor prognostic factor in colorectal carcinoma; however, its molecular basis has not been defined. This study aimed to assess the expression of molecular markers in EMVI positive colorectal carcinoma to understand their tumor microenvironment. METHODS: Immunohistochemistry was performed on tissue microarrays of surgically resected colorectal cancer specimens for immunological markers, and BRAFV600E mutation (and on the tissue blocks for mismatch repair proteins). Automated quantification was used for CD8, LAG3, FOXP3, PU1, and CD163, and manual quantification was used for PDL1, HLA I markers (beta-2 microglobulin, HC10), and HLA II. The Wilcoxon rank-sum test was used to compare EMVI positive and negative tumors. A logistic regression model was fitted to assess the predictive effect of biomarkers on EMVI. RESULTS: There were 340 EMVI positive and 678 EMVI negative chemo naïve tumors. PDL1 was barely expressed on tumor cells (median 0) in the entire cohort. We found a significantly lower expression of CD8, LAG3, FOXP3, PU1 cells, PDL1 positive macrophages, and beta-2 microglobulin on tumor cells in the EMVI positive subset (p ≤ 0.001). There was no association of BRAFV600E or deficient mismatch repair proteins (dMMR) with EMVI. PU1 (OR 0.8, 0.7-0.9) and low PDL1 (OR 1.6, 1.1-2.3) independently predicted EMVI on multivariate logistic regression among all biomarkers examined. CONCLUSION: There is a generalized blunting of immune response in EMVI positive colorectal carcinoma, which may contribute to a worse prognosis. Tumor-associated macrophages seem to play the most significant role in determining EMVI.

Impact of Bundled Payment Care Improvement Initiative on Health Care Expenditure in Major Bowel Procedures.

BACKGROUND: The Bundled Payments for Care Improvement initiative links payments for Medicare beneficiaries during an episode of care (90 days from index surgery). OBJECTIVE: This study aimed to determine whether major bowel participating Bundled Payments for Care Improvement organizations experience greater cost savings for colectomy while maintaining satisfactory quality outcomes compared to nonparticipating organizations. DESIGN: This is an Analysis of all Bundled Payments for Care Improvement participating hospitals for major bowel procedures (major bowel group) and propensity score-matched against Bundled Payments for Care Improvement organizations that do not include major bowel procedures (nonmajor bowel group) and those that do not participate in any Bundled Payments for Care Improvement program (non-Bundled Payments for Care Improvement group). SETTING: Programs accepting Medicare and Medicaid in the United States. PATIENTS: Patients included were major bowel cases in the Medicare Standard Analytic file within Medicare Severity Diagnosis-Related Groups 329-331 at participating facilities between January 1, 2011, and June 30, 2016. MAIN OUTCOME MEASURES: Main outcome measures included average total care expenditure and quality of care (length of stay, morbidity, and mortality) from 3 days preoperatively to 90 days postoperatively. RESULTS: We abstracted 7609 major bowel episodes from 23 major bowel group facilities, 21,872 episodes from nonmajor bowel-matched hospitals, and 19,383 episodes from non-Bundled Payments for Care Improvement-matched hospitals. From the baseline (January 2011 to June 2012) to final period (July 2015 to June 2016), we noted a $2955 average reduction in care expenditures. The largest decrease in average total episode expenditure occurred within the major bowel group (14% reduction) compared to the other groups (6% reduction for nonmajor bowel and 5% reduction for non-Bundled Payments for Care Improvement). Utilizing a generalized estimating equation to adjust for patient demographics, comorbidities, and hospital characteristics, the average total episode expenditure for the major bowel group decreased by $4885 (95% CI $4838-$4932; p < 0.001) compared to $2050 (95% CI $2038-$2061) for the non-Bundled Payments for Care Improvement group. All groups had similar reductions in length of stay, 30-day and 90-day complication rates, and readmission rates. LIMITATIONS: Analyses were limited by the retrospective nature of the study. CONCLUSIONS: Bundled Payments for Care Improvement participation for major bowel procedures resulted in a greater decrease in average total cost per episode of care than in nonparticipating hospitals without compromise in quality of care. See Video Abstract at http://links.lww.com/DCR/B837.IMPACTO DE LA INICIATIVA BUNDLED PAYMENT AGRUPADOS PARA LA MEJORA DE LA ATENCIÓN DEL GASTO SANITARIO EN LOS PROCEDIMIENTOS INTESTINALES MAYORESANTECEDENTES:La iniciativa de Bundled Payment para la mejora de la atención vincula los pagos para los beneficiarios de Medicare durante un episodio de atención (90 días desde la cirugía índice).OBJETIVO:Determinar si las principales organizaciones de Bundled Payment para el mejoramiento de la atención relacionados a los procedimientos intestinales experimentan mayores ahorros en los costos para una colectomía manteniendo resultados satisfactorios de calidad en comparación con las organizaciones no participantes.DISEÑO:Análisis de todos los hospitales participantes del programa Bundled Payment para la mejora de la atención para procedimientos intestinales mayores (grupo que incluyen procedimientos intestinales mayores) y puntaje de propensión comparado con las organizaciones que no incluyen dichos procedimientos (grupo que no incluye procedimientos intestinales mayores) y aquellos que no participan en ningún programa de Bundled Payment para la mejora de la atención (grupo no BPCI).MARCO:Programas que aceptan Medicare y Medicaid en los Estados Unidos.PACIENTES:Casos intestinales mayores en el archivo analítico estándar de Medicare dentro de los grupos relacionados con el diagnóstico 329-331 en los centros participantes entre el 1/1/2011-30/6/2016.PRINCIPALES MEDIDAS DE RESULTADO:Gasto total promedio y calidad de la atención (duración de la estadía, morbilidad, mortalidad) desde los 3 días preoperatorio hasta los 90 días postoperatorio.RESULTADOS:Hemos extraído 7609 episodios intestinales mayores de 23 instalaciones del grupo que incluyen procedimientos intestinales mayores, 21.872 episodios de hospitales del grupo que no incluyen procedimientos intestinales mayores y 19.383 episodios de hospitales del grupo no BPCI. Desde la línea de base (1/2011 - 6/2012) hasta el período final (7/2015 - 6/2016), notamos una reducción promedio de $2955 en los gastos de atención. La mayor disminución en el gasto promedio total por episodios ocurrió dentro del grupo que incluyen intestinales mayores (14% de reducción) en comparación con los otros grupos (6% de reducción para el grupo que no incluyen procedimientos intestinales mayores, 5% de reducción para el no BPCI). Utilizando una ecuación de estimación generalizada para ajustar los datos demográficos del paciente, las comorbilidades y las características del hospital, el gasto total promedio por episodio para el grupo que incluyen procedimientos intestinales mayores disminuyó en $ 4885 (IC del 95%: $4838-4932; p <0,001) en comparación con $2050 (IC del 95%: $2038-2061) para el grupo que no pertenece al programa BPCI. Todos los grupos tuvieron reducciones similares en la duración de la estancia, tasas de complicaciones de 30/90 días y de readmisión.LIMITACIONES:Análisis limitados por la naturaleza retrospectiva del estudio.CONCLUSIONES:La participación de Bundled Payment para la mejora de la atención en aquellos procedimientos intestinales mayores resultó en una disminución mayor en el costo total promedio por episodio de atención que en los hospitales no participantes, sin comprometer la calidad de la atención. Consulte Video Resumen en http://links.lww.com/DCR/B837. (Traducción-Dr Osvaldo Gauto).

Tumour genotypes account for survival differences in right- and left-sided colon cancers.

AIM: We sought to identify genetic differences between right- and left-sided colon cancers and using these differences explain lower survival in right-sided cancers. METHOD: A retrospective review of patients diagnosed with colon cancer was performed using The Cancer Genome Atlas, a cancer genetics registry with patient and tumour data from 20 North American institutions. The primary outcome was 5-year overall survival. Predictors for survival were identified using directed acyclic graphs and Cox proportional hazards models. RESULTS: A total of 206 right- and 214 left-sided colon cancer patients with 84 recorded deaths were identified. The frequency of mutated alleles differed significantly in 12 of 25 genes between right- and left-sided tumours. Right-sided tumours had worse survival with a hazard ratio of 1.71 (95% confidence interval 1.10-2.64, P = 0.017). The total effect of the genetic loci on survival showed five genes had a sizeable effect on survival: DNAH5, MUC16, NEB, SMAD4, and USH2A. Lasso-penalized Cox regression selected 13 variables for the highest-performing model, which included cancer stage, positive resection margin, and mutated alleles at nine genes: MUC16, USH2A, SMAD4, SYNE1, FLG, NEB, TTN, OBSCN, and DNAH5. Post-selection inference demonstrated that mutations in MUC16 (P = 0.01) and DNAH5 (P = 0.02) were particularly predictive of 5-year overall survival. CONCLUSIONS: Our study showed that genetic mutations may explain survival differences between tumour sites. Further studies on larger patient populations may identify other genes, which could form the foundation for more precise prognostication and treatment decisions beyond current rudimentary TNM staging.

Prescribing as affective clinical practice: Transformations in sexual health consultations through HIV pre-exposure prophylaxis.

New medicines can transform routines and priorities in clinical practice, but how do clinicians think and feel about these changes, and how does it affect their work? In Australia, the HIV prevention regimen pre-exposure prophylaxis (PrEP) has been rapidly rolled out, transforming the sexual cultures and practices of users, but less attention has been given to the ways PrEP has reconfigured clinical practice. This paper draws on 28 qualitative semi-structured interviews conducted between 2019 and 2020 with PrEP-providing doctors and nurses in Australia to consider how they have affectively engaged with PrEP and put it into practice. Through a reflexive thematic analysis, we explore how clinicians adapted to PrEP, how the field of HIV prevention has been transformed, and how these developments have changed how clinicians approach patients. While the introduction of PrEP was initially received with uncertainty and shock, clinicians described PrEP as enjoyable to prescribe, and better aligned with the moral duties of sexual health consultations than existing HIV prevention strategies like condoms. Through approaching clinical work as an 'affective practice', we argue for attending not only to how new interventions change expectations and practices, but also how these changes are felt and valued by clinicians.

Clinician imaginaries of HIV PrEP users in and beyond the gay community in Australia.

Through the development and implementation of HIV pre-exposure prophylaxis (PrEP), the characteristics of PrEP users have been configured in a range of ways. Drawing on the concept of 'imaginaries', we consider how clinicians imagine PrEP users and related communities. We conducted 28 semi-structured interviews in 2019-2020 with PrEP-providing clinicians based in New South Wales and Western Australia. Participants included general practitioners, sexual health nurses and sexual health doctors. We inductively developed three themes through a reflexive thematic analysis: 'PrEP users as 99% gay men/MSM', 'The informed and connected PrEP user', and 'Condom users in the PrEP era'. Participants imagined PrEP users primarily as gay men, and so we focused on how gay community was imagined in relation to PrEP users. Users were imagined as supporting one another to use PrEP effectively, but some were imagined as threatening norms of condom use amongst gay community. Analysing clinician imaginaries of PrEP users reveals insight into how clinicians speculate about and engage with changing community norms related to condom use and accessing PrEP. These imaginaries reveal ongoing tensions about who is believed to be best suited to PrEP, and PrEP's impact on norms of conduct in imagined biosocial communities like gay men.

Navigating trans visibilities, trauma and trust in a new cervical screening clinic.

Trans and gender diverse people are globally recognised as being under-served in clinical services, with significant implications for their health. During a national reorientation of the Australian cervical screening programme - from Papanicolaou smears to human papillomavirus screening - we conducted interviews with 12 key informants in cancer policy, sexual and reproductive health and trans health advocacy to understand how trans people's needs and experiences were being accounted for and addressed in health policy and practice. Themes captured the complexities of increasing visibility for trans people, including men and non-binary people with a cervix. These complexities reflect the extensive system and cultural change required in asking policymakers and practitioners to think differently about who is at risk of a disease typically associated with cisgender women. Informants drew on the language of trauma to explain the resistance many trans people feel when engaging with clinical services, particularly relating to sexual and reproductive health. In doing so, they argued for increasing resources and processes to elicit trans people's willingness to put their trust in such services. Thinking critically about the relationship between the politics of trans visibilities, trauma and trust can support effective and inclusive approaches to transgender health.

Sustaining sexual and reproductive health through COVID-19 pandemic restrictions: qualitative interviews with Australian clinicians.

BACKGROUND: The sexual and reproductive health care of people with HIV and those at risk of HIV has largely been delivered face-to-face in Australia. These services adapted to the coronavirus disease 2019 (COVID-19) pandemic with a commitment to continued care despite major impacts on existing models and processes. Limited attention has been paid to understanding the perspectives of the sexual and reproductive health care workforce in the research on COVID-19 adaptations. METHODS: Semi-structured interviews were conducted between June and September 2021 with 15 key informants representing a diverse range of service settings and professional roles in the Australian sexual and reproductive health sector. Inductive themes were generated through a process of reflexive thematic analysis, informed by our deductive interest in clinical adaptations. RESULTS: The major adaptations were: triage (rapidly adapting service models to protect the most essential forms of care); teamwork (working together to overcome ongoing threats to service quality and staff wellbeing), and the intwined themes of telehealth and trust (remaining connected to marginalised communities through remote care). Despite impacts on care models and client relationships, there were sustained benefits from the scaleup of remote care, and attention to service safety, teamwork and communication. CONCLUSIONS: Attending to the experiences of those who worked at the frontline of the COVID-19 response provides essential insights to inform sustained, meaningful system reform over time. The coming years will provide important evidence of longer-term impacts of COVID-19 interruptions on both the users and providers of sexual and reproductive health services.