Citations

Abstract Background/Aims In shared decision-making conversations, patients with or at risk of osteoporosis and their clinicians collaborate to decide which drug treatments fit best for each person. The Perceptions and Practicalities Approach (PAPA) specifies three core considerations of drug uptake and commitment: 1) patient’s perceived personal need for treatment (necessity beliefs). 2) patient concerns about the potential adverse consequences of drugs (e.g. side effects). 3) practical difficulties (e.g. limitations in capacity and resources). This study aims to explore how discussions about perceptions and practicalities of osteoporosis drug treatment arise and evolve in the context of clinical consultations about osteoporosis. Methods Secondary analysis of 38 video-recorded primary care consultations from a Mayo Clinic trial evaluating the Osteoporosis Choice Decision Aid. Video-recorded consultations included ‘usual care’ (n = 24) and decision aid (n = 14). Patient participants were aged 50 and over with osteopenia or osteoporosis not already receiving drug treatment. A quantitative coding scheme, informed by the PAPA, was developed to extract: i) how clinicians framed the ‘problem’ of osteoporosis, including: bone density results, fracture risk, physical impact, social impact, or psychological impact of fracture. ii) whether clinicians asked about the patients’ views of osteoporosis, patients own bone health, and the necessity, concerns, or practical issues associated with osteoporosis drugs. iii) whether clinicians personalised discussions about osteoporosis drugs to patients perceived: importance or need, side effects or harms, or practical issues. Two independent study team members dual extracted data, with a third member resolving discrepancies. Extracted data was summarised using descriptive statistics. Results Commonly, clinicians framed osteoporosis using the patient’s bone density results (n = 38,100%) and fracture risk (n = 30,79%). In contrast, few clinicians acknowledged the potential physical impacts of fracture (n = 5,13%), with no clinicians discussing the possible psychological or social impacts. Clinicians asked 24 questions to elicit patient views in 16 of the 38 encounters (42%, range 0-4 questions per consult). The 24 questions concerned patient views about osteoporosis (n = 1,4%), their bone health (n = 5,21%), or the necessity (n = 1,4%), concerns (n = 2,8%), or practical issues associated with osteoporosis drugs (n = 2,8%). Importantly, 14 consultations (37%) contained no questions to elicit patient views. Across the 38 consultations, clinicians personalised information about the patient’s need for osteoporosis drugs in 15 consultations (39%), with less personalisation about the side effects/harms (n = 10,26%), or practical issues (n = 6,16%) associated with osteoporosis drugs. Conclusion Clinical consultations rarely considered key personal determinants of osteoporosis drug uptake and commitment. Even when clinicians used an osteoporosis decision aid, few discussions specifically elicited or addressed patients’ personal treatment necessity beliefs, concerns and practical difficulties. Additionally, clinicians seldom acknowledged the potential physical and psychosocial impacts of osteoporosis. The findings demonstrate the need for multicomponent interventions, incorporating the PAPA-based approach, to facilitate shared decision-making that takes account of patient perceptions and practicalities. Disclosure A.W. Hawarden: Grants/research support; AH is funded by a Versus Arthritis Clinical Doctoral Fellowship (grant reference 227260). L. Bullock: None. M. León-García: Grants/research support; ML-G had financial support from the Spanish Health Institute Carlos III (ISCIII) co-funded by the European Regional Development Fund (Grant number: F18/00014).. S.A. Hartasanchez: None. I. Hargraves: None. R. Horne: None. A. Maraboto: None. M. Kunneman: Grants/research support; MK had financial support from the Dutch Research Council (NWO) and The Netherlands Organisation for Health Research and Development (ZonMw) (#016.196.138). C. Jinks: Grants/research support; CJ is part funded by NIHR Applied Research Collaboration (ARC) West Midlands. Z. Paskins: Grants/research support; ZP is funded by the National Institute for Health Research (NIHR) [Clinician Scientist Award (CS-2018-18-ST2-010)/NIHR Academy].

AimsDue to its rarity and non‐specific clinical and pathological features, low‐grade adenosquamous carcinoma (LGASC) of the breast continues to pose diagnostic challenges. Unlike other triple‐negative breast carcinomas, LGASC tends to have an indolent clinical behaviour. It is essential to recognise this lesion for accurate diagnosis and appropriate management.Methods and resultsTwenty‐five cases of LGASC were identified in our archives and collaborating institutes. Cases of LGASC with dominant coexisting other type carcinomas were excluded. We studied the clinical presentation, morphological features, patterns of the commonly used immunohistochemical stains and follow‐up. In our cohort, LGASC was commonly located at the outer aspect of the breast and associated with intraductal papilloma. The morphology of LGASC is characterised by infiltrating small glands and nests with variable squamous differentiation. We also found cuffing desmoplastic (fibrolamellar) stromal change in 75% of patients and peripheral lymphocytic aggregates in 87.5% of patients. P63 and smooth muscle myosin (SMM) were the most common myoepithelial markers used to assist in diagnosis. P63 often stained peripheral tumour cells surrounding invasive glands (circumferential staining in 80% of the cases), mimicking myoepithelial cells. It also stained the small nests with squamous differentiation. However, SMM was negative in 63% of the cases. The vast majority of our cases were triple‐negative; only a few had focal and weak expressions of ER and PR. One patient who did not have excision developed lymph node metastasis. Most patients underwent excision or mastectomy with negative margins as surgical treatment; there were no recurrences or metastases in these patients with clinical follow‐ups up to 108 months.ConclusionsLGASC has some unique, although not entirely specific, morphological features and immunohistochemical staining patterns. Fibrolamellar stromal change, peripheral lymphocytic aggregates and variable staining of p63 and SMM are valuable features to facilitate the diagnosis.

Sex hormone concentrations, particularly testosterone, are primary determinants of sex-based differences in athletic and sports performance, and this relationship may inform fair competition and participation for athletes. This article describes the sex-based dichotomy in testosterone and the implications for sex-based differences in individual sports performance, including factors that relate to athletic performance for transgender individuals, and areas of future investigation.

Background The association between growth differentiation factor-15 concentrations and cardiovascular disease has been well described. The study hypothesis was that growth differentiation factor-15 may help cardiac risk stratification in noncardiac surgical patients, in addition to clinical evaluation. Methods The objective of the study was to determine whether preoperative serum growth differentiation factor-15 is associated with the composite primary outcome of myocardial injury after noncardiac surgery and vascular death at 30 days and can improve cardiac risk prediction in noncardiac surgery. This is a prospective cohort study of patients 45 yr or older having major noncardiac surgery. The association between preoperative growth differentiation factor-15 and the primary outcome was determined after adjusting for the Revised Cardiac Risk Index. Preoperative N-terminal-pro hormone brain natriuretic peptide was also added to compare predictive performance with growth differentiation factor-15. Results Between October 27, 2008, and October 30, 2013, a total of 5,238 patients were included who had preoperative growth differentiation factor-15 measured (median, 1,325; interquartile range, 880 to 2,132 pg/ml). The risk of myocardial injury after noncardiac surgery and vascular death was 99 of 1,705 (5.8%) for growth differentiation factor-15 less than 1,000 pg/ml, 161 of 1,332 (12.1%) for growth differentiation factor-15 1,000 to less than 1,500 pg/ml, 302 of 1476 (20.5%) for growth differentiation factor-15 1,500 to less than 3,000 pg/ml, and 247 of 725 (34.1%) for growth differentiation factor-15 concentrations 3,000 pg/ml or greater. Compared to patients who had growth differentiation factor-15 concentrations less than 1,000 pg/ml, the corresponding adjusted hazard ratio for each growth differentiation factor-15 category was 1.93 (95% CI, 1.50 to 2.48), 3.04 (95% CI, 2.41 to 3.84), and 4.8 (95% CI, 3.76 to 6.14), respectively. The addition of growth differentiation factor-15 improved cardiac risk classification by 30.1% (301 per 1,000 patients) compared to Revised Cardiac Risk Index alone. It also provided additional risk classification beyond the combination of preoperative N-terminal-pro hormone brain natriuretic peptide and Revised Cardiac Risk Index (16.1%; 161 per 1,000 patients). Conclusions Growth differentiation factor-15 is strongly associated with 30-day risk of major cardiovascular events and significantly improved cardiac risk prediction in patients undergoing noncardiac surgery. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Abstract Background: Human Papillomavirus (HPV) vaccination rates remain low in the U.S., particularly among minorities and low-income patients. In 2014, a Mayo Clinic study of uninsured, low-income, working, Volunteer in Medicine (VIM) Clinic patients in Jacksonville, Florida found a statistically significant lower awareness of HPV (50.3% vs 63.6%) and the HPV vaccine (32.1% vs 62.7%) than the national population. As a result, our team collaborated with Merck to develop a free HPV vaccination program and video education campaign for VIM patients. Methods: We assessed VIM patients HPV vaccination knowledge, awareness, and prevalence of hesitancy towards receiving the vaccine. VIM patients (ages 18-45) with no previous history of HPV vaccination were invited to participate in this study. The Parents Attitudes about Childhood Vaccines (PACV) survey was used to evaluate vaccine hesitancy. Patients who declined the HPV vaccine were shown an educational video to assess effectiveness in persuading patients’ opinion. Each participant received a vaccine hesitancy PACV score, which was compared with their vaccine disposition. Mayo Clinic IRB approval of the study was obtained. Results: Our analysis included 43 patients (34 females, 9 males) with a median age of 40 (age range 27- 45). Patients had overall knowledge of HPV of 88.4%, with 69.8% having heard of the HPV vaccine. 85.7% PACV survey respondents were deemed non-hesitant (PACV scores 0-49), and 80.6% of the non-hesitant subset (29/36) agreed to undergo vaccination. The average PACV score of vaccine-interested participants was lower (25.2) than the average of participants not interested in the vaccine (36.7). Black participants had a statistically significant higher PACV score than White participants. The PACV scores of individuals who were already familiar with the HPV vaccine were significantly lower than those of participants who were unfamiliar with the HPV vaccine. Only 20% (2/10) of individuals, who had previously declined vaccination, agreed to receive the HPV vaccine after viewing the HPV educational video. Of the 33 participants who agreed to receive the free HPV vaccine, only 9 (27.3%) completed all three doses. Conclusions: HPV vaccine awareness and knowledge at VIM increased compared to the 2014 cohort. Vaccine hesitancy was not observed in most patients, yet video education was effective in only a small portion of patients with vaccine hesitancy. Additionally, a minority of patients who agreed to receive the free HPV vaccine series completed all three doses. Our results suggests that free HPV vaccination and video education is not sufficient to achieve adequate vaccination rates among low-income uninsured young adults, nor overcoming vaccine hesitancy. Innovative measures are warranted to improve vaccination rates in this population. Citation Format: Hiram Diaz, Gerardo Colon-Otero, Laura M. Pacheco-Spann, Christopher C. DeStephano, Sandra Casanova-Leyva. Assessing knowledge, vaccine hesitancy, and completion rates of free HPV vaccination in uninsured/underinsured low-income patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5539.

AbstractIntroductionFor too many people, their care plans are designed without fully accounting for who they are, the lives they live, what matters to them or what they aspire to achieve. We aimed to summarize instruments capable of measuring dimensions of patient–clinician collaboration to make care fit.MethodsWe systematically searched several databases (Medline, Embase, Cochrane, Scopus and Web of Science) from inception to September 2021 for studies using quantitative measures to assess, evaluate or rate the work of making care fit by any participant in real‐life clinical encounters. Eligibility was assessed in duplicate. After extracting all items from relevant instruments, we coded them deductively on dimensions relevant to making care fit (as presented in a recent Making Care Fit Manifesto), and inductively on the main action described.ResultsWe included 189 papers, mostly from North America (N = 83, 44%) and in the context of primary care (N = 54, 29%). Half of the papers (N = 88, 47%) were published in the last 5 years. We found 1243 relevant items to assess efforts of making care fit, included within 151 instruments. Most items related to the dimensions ‘Patient‐clinician collaboration: content’ (N = 396, 32%) and ‘Patient‐clinician collaboration: manner’ (N = 382, 31%) and the least related to ‘Ongoing and iterative process’ (N = 22, 2%) and in ‘Minimally disruptive of patient lives’ (N = 29, 2%). The items referred to 27 specific actions. Most items referred to ‘Informing’ (N = 308, 25%) and ‘Exploring’ (N = 93, 8%), the fewest items referred to ‘Following up’, ‘Comforting’ and ‘Praising’ (each N = 3, 0.2%).DiscussionMeasures of the work that patients and clinicians do together to make care fit focus heavily on the content of their collaborations, particularly on exchanging information. Other dimensions and actions previously identified as crucial to making care fit are assessed infrequently or not at all. The breadth of extant measures of making care fit and the lack of appropriate measures of this key construct limit both the assessment and the successful implementation of efforts to improve patient care.Patient ContributionPatients and caregivers from the ‘Making care fit Collaborative’ were involved in drafting the dimensions relevant to patient–clinician collaboration.

AbstractObjectivesDetection of α‐synuclein aggregates by seed amplification is a promising Parkinson disease biomarker assay. Understanding intraindividual relationships of α‐synuclein measures could inform optimal biomarker development. The objectives were to test accuracy of α‐synuclein seed amplification assay in central (cerebrospinal fluid) and peripheral (submandibular gland) sources, compare to total α‐synuclein measures, and investigate within‐subject relationships.MethodsThe Systemic Synuclein Sampling Study aimed to characterize α‐synuclein in multiple tissues and biofluids within Parkinson disease subjects (n = 59) and compared to healthy controls (n = 21). Motor and non‐motor measures and dopamine transporter scans were obtained. Four measures of α‐synuclein were compared: seed amplification assay in cerebrospinal fluid and formalin‐fixed paraffin‐embedded submandibular gland, total α‐synuclein quantified in biofluids using enzyme‐linked immunoassay, and aggregated α‐synuclein in submandibular gland detected by immunohistochemistry. Accuracy of seed amplification assay for Parkinson disease diagnosis was examined and within‐subject α‐synuclein measures were compared.ResultsSensitivity and specificity of α‐synuclein seed amplification assay for Parkinson disease diagnosis was 92.6% and 90.5% in cerebrospinal fluid, and 73.2% and 78.6% in submandibular gland, respectively. 25/38 (65.8%) Parkinson disease participants were positive for both cerebrospinal fluid and submandibular gland seed amplification assay. Comparing accuracy for Parkinson disease diagnosis of different α‐synuclein measures, cerebrospinal fluid seed amplification assay was the highest (Youden Index = 83.1%). 98.3% of all Parkinson disease cases had ≥1 measure of α‐synuclein positive.Interpretationα‐synuclein seed amplification assay (cerebrospinal fluid>submandibular gland) had higher sensitivity and specificity compared to total α‐synuclein measures, and within‐subject relationships of central and peripheral α‐synuclein measures emerged.

Abstract Objective Flares of autoimmune rheumatic diseases (AIRDs) following COVID-19 vaccination are a particular concern in vaccine-hesitant individuals. Therefore, we investigated the incidence, predictors and patterns of flares following vaccination in individuals living with AIRDs, using global COVID-19 Vaccination in Autoimmune Diseases (COVAD) surveys. Methods The COVAD surveys were used to extract data on flare demographics, comorbidities, COVID-19 history, and vaccination details for patients with AIRDs. Flares following vaccination were identified as patient-reported (a), increased immunosuppression (b), clinical exacerbations (c) and worsening of PROMIS scores (d). We studied flare characteristics and used regression models to differentiate flares among various AIRDs. Results Of 15 165 total responses, the incidence of flares in 3453 patients with AIRDs was 11.3%, 14.8%, 9.5% and 26.7% by definitions a–d, respectively. There was moderate agreement between patient-reported and immunosuppression-defined flares (K = 0.403, P = 0.022). Arthritis (61.6%) and fatigue (58.8%) were the most commonly reported symptoms. Self-reported flares were associated with higher comorbidities (P = 0.013), mental health disorders (MHDs) (P < 0.001) and autoimmune disease multimorbidity (AIDm) (P < 0.001). In regression analysis, the presence of AIDm [odds ratio (OR) = 1.4; 95% CI: 1.1, 1.7; P = 0.003), or a MHD (OR = 1.7; 95% CI: 1.1, 2.6; P = 0.007), or being a Moderna vaccine recipient (OR = 1.5; 95% CI: 1.09, 2.2; P = 0.014) were predictors of flares. Use of MMF (OR = 0.5; 95% CI: 0.3, 0.8; P = 0.009) and glucocorticoids (OR = 0.6; 95% CI: 0.5, 0.8; P = 0.003) were protective. A higher frequency of patients with AIRDs reported overall active disease post-vaccination compared with before vaccination (OR = 1.3; 95% CI: 1.1, 1.5; P < 0.001). Conclusion Flares occur in nearly 1 in 10 individuals with AIRDs after COVID vaccination; people with comorbidities (especially AIDm), MHDs and those receiving the Moderna vaccine are particularly vulnerable. Future avenues include exploring flare profiles and optimizing vaccine strategies for this group.

The preventive efficacy of MUC1-specific DNA immunization on inflammation-driven colon carcinogenesis in human MUC1 transgenic (MUC1.Tg) mice was investigated. Mice were vaccinated with MUC1 DNA mixed with autologous bone-marrow-derived dendritic cells (BMDCs), and then colonic tumors were induced by azoxymethane (AOM) injection and oral administration of dextran sulfate sodium (DSS). Two types of tumors, squamous metaplasia and tubular adenoma, were observed. Both expressed high levels of MUC1 as indicated by the binding of anti-MUC1 antibodies with different specificities, whereas MUC1 expression was not detected in normal colonic mucosa. When mice were immunized with MUC1 DNA + BMDCs, tumor incidence, tumor number, and tumor size were significantly reduced. In contrast, vaccination with MUC1 DNA alone or BMDCs alone was ineffective in reducing tumor burden. Inflammation caused by DSS was not suppressed by the MUC1 DNA + BMDCs vaccination. Furthermore, MUC1 protein expression levels, as judged by anti-MUC1 antibody binding in tumors grown after vaccination, did not significantly differ from the control. In conclusion, an inflammation-driven carcinogenesis model was established in MUC1.Tg mice, closely resembling human colon carcinogenesis. In this model, vaccination with MUC1 DNA + BMDCs was effective in overriding MUC1 tolerance and reducing the tumor burden by a mechanism not affecting the level of colonic inflammation.

AbstractOur objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high‐grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi‐institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36–3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11–2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.