Unmet needs and barriers in venous thromboembolism education and awareness among people living with cancer: A global survey.

BACKGROUND: Venous thromboembolism (VTE) is a major preventable cause of morbidity, disability, and mortality in subjects with cancer. A global appraisal of cancer-associated VTE education and awareness is not available. OBJECTIVES: To evaluate VTE-related education, awareness, and unmet needs from the perspective of people living with cancer using a quantitative and qualitative approach. PATIENTS/METHODS: This cross-sectional study used data from an online-based survey covering multidimensional domains of cancer-associated VTE. Data are presented descriptively. Potential differences across participant subgroups were explored. RESULTS: Among 2262 patients with cancer from 42 countries worldwide, 55.3% received no VTE education throughout their cancer journey, and an additional 8.2% at the time of VTE diagnosis only, leading to 63.5% receiving none or inappropriately delayed education. When education was delivered, only 67.8% received instructions to seek medical attention in case of VTE suspicion, and 36.9% reported scarce understanding. One third of participants (32.4%) felt psychologically distressed when becoming aware of the potential risks and implications connected with cancer-associated VTE. Most responders (78.8%) deemed VTE awareness highly relevant, but almost half expressed concerns on the quality of education received. While overall consistent, findings in selected survey domains appeared to numerically differ across age groups, ethnicity, continent of residence, educational level, metastatic status, and VTE history. CONCLUSIONS: This study involving a large and diverse population of individuals living with cancer identifies important unmet needs in VTE-related education, awareness, and support across healthcare systems globally. These findings unveil multilevel opportunities to expedite patient-centered care in cancer-associated VTE prevention and management.

Optimizing antithrombotic therapy in patients with coexisting cardiovascular and gastrointestinal disease.

Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases.

Alternative dosing regimen of exemestane in a randomized presurgical trial: the role of obesity in biomarker modulation.

In a 3-arm presurgical trial, four-six weeks exemestane 25 mg three times/week (TIW) was non-inferior to 25 mg/day (QD) in suppressing circulating estradiol in postmenopausal women with ER-positive breast cancer. Since obesity may decrease exemestane efficacy, we analyzed changes in sex steroids, adipokines, Ki-67, and drug levels in relation to obesity. Postmenopausal women with early-stage ER-positive breast cancer were randomized to either exemestane 25 mg QD (n = 57), 25 mg TIW (n = 57), or 25 mg/week (QW, n = 62) for 4-6 weeks before breast surgery. Serum and tissue pre- and post-treatment biomarkers were stratified by body mass index (BMI)< or ≥30 kg/m2. Post-treatment median exemestane and 17-OH exemestane levels were 5-6 times higher in the QD arm compared to the TIW arm. For obese women, TIW maintained comparable reductions to QD in systemic estradiol levels, although the reduction in estrone was less with the TIW regimen. There was less suppression of SHBG with the TIW versus the QD dose schedule in obese women which should result in less systemic bioavailable estrogens. Metabolically, the effect of the TIW regimen was similar to the QD regimen for obese women in terms of leptin suppression and increase in the adiponectin-leptin ratio. Reduction in tissue Ki-67 was less for obese women on the TIW regimen than QD, although changes were similar for non-obese women. Our findings suggest that TIW exemestane should be explored further for primary cancer prevention in both normal weight and obese cohorts.

Cytoreductive Surgery with Bidirectional Intraoperative Chemotherapy (BDIC) Using Intravenous Ifosfamide Plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients with Peritoneal Sarcomatosis: A Retrospective Cohort Study.

BACKGROUND: Peritoneal sarcomatosis (PS) is a rare tumor with limited therapeutic options. Bidirectional intraoperative chemotherapy (BDIC) using intravenous ifosfamide and doxorubicin-based hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) is an emerging treatment for peritoneal malignancies. PATIENTS AND METHODS: Patients with PS who underwent CRS/BDIC using intravenous ifosfamide and HIPEC from January 2017 to July 2021 were retrospectively analyzed. The last follow-up date was May 2022. RESULTS: A total of 29 patients were included. Overall survival (OS) rates at 6, 12, 24, and 48 months after CRS/BDIC were 93.1%, 89.2%, 81.4%, and 73.3%, respectively. As of May 2022, 6 patients (20.6%) had died, including four (13.8%) with a proven recurrent tumor and two with incomplete tumor resection [completeness of cytoreduction (CC)-2 or CC-3]. Of the 20 patients (68.9%) with CC-0 or CC-1, 7 had locoregional tumor recurrence without distant metastasis, whereas the other 13 were alive with no evidence of recurrent tumor in May 2022. Disease recurrence rates were 15% at 6 months and 35% at 12, 24, and 48 months after CRS/BDIC. Clavien-Dindo class ≥ IIIa complications developed in 9 patients (31.0%) with no deaths. Leukopenia occurred in 5 patients (17.2%) and thrombocytopenia in 12 patients (41.3%); these hematologic abnormalities resolved. A total of 9 (31.0%) patients developed nephrotoxicity; all recovered except one, who progressed to chronic kidney disease. CONCLUSIONS: CRS/BDIC using intravenous ifosfamide and doxorubicin-based HIPEC is a potentially effective treatment for PS and has an acceptable rate of complications.

Total hip arthroplasty for adult patients with hip arthritis in Jordan: clinical profiles and patient characteristics.

PURPOSE: Total Hip Arthroplasty (THA) is one of the most commonly performed orthopaedic surgeries, with hip arthritis being the main indication. This procedure is usually performed when other non-surgical methods fail to relieve patients' hip pain and improve their quality of life. However, limited information exists to identify and compare the demographics and clinical characteristics of patients undergoing this procedure in Jordan. This study aims to identify these demographic and clinical characteristics and compare the findings in terms of gender differences. METHODOLOGY: This is a retrospective study that analysed the hospital records of 650 patients undergoing THA in tertiary referral hospital in Jordan over a four-year period from January 2019 to December 2022. The collected data were classified into three categories: demographic characteristics, perioperative variables, and patients' related health profiles. IBM's Statistical Package for the Social Sciences (SPSS) version 23 software (IBM, USA) and descriptive analysis were used for data analysis. RESULTS: Two-thirds of the sample studied were female (63.4%). In terms of bleeding profiles, the mean intraoperative blood loss was 542 millilitres. The major indication for THA was degenerative hip arthritis (50.5%), followed by hip dysplasia (40.3%).. Comparing the findings of the two gender groups, females were more likely to have degenerative and dysplastic hip arthritis (221 and 157, p = 0.04 and p = 0.1, respectively) when compared to males. Although males were more likely to lose more blood during the surgery (557 ml vs. 533 ml, p = 0.33, females needed more blood transfusions both during (21 vs. 6 patients, p = 0.12) and after the surgery (57 vs. 16 patients, p = 0.006). Furthermore, females were more likely to have comorbidities such hypertension (293 vs. 179 patients, p = 0.20), and hypothyroidism (313 vs 187, p = 0.36), and diabetes (85 vs. 38 patients, p = 0.15), among many other health conditions. However, in the study sample, male smokers outnumbered female smokers (132 vs. 63). CONCLUSION: Gender highly impacted the immediate surgical outcomes of patients who underwent THA. Females were more likely to need blood transfusions both during and after the surgery and had lower post-operative haemoglobin readings. In addition, females had more comorbidities and degenerative hip osteoarthritis. We believe that raising awareness about comorbidity management, preoperative smoking cessation, and perioperative blood transfusion management can improve medical and surgical outcomes.

Availability of medical and endovascular therapies for venous thromboembolism: a global survey for World Thrombosis Day.

BACKGROUND: Data on availability, affordability, and accessibility is key for the planning of global strategies to reduce the burden of venous thromboembolism (VTE). OBJECTIVES: A survey was conducted for the 10th anniversary of World Thrombosis Day to assess the availability of VTE therapies worldwide and challenges in uniform implementation. METHODS: We gathered information on the approval status, availability, utilization, occurrence of shortages, and spread of medical and interventional therapies for VTE. Furthermore, we collected information by accessing or contacting national or continental medicines agencies, manufacturers or distributors, and online drug repositories. RESULTS: We obtained data from a total of 69 countries: 33 countries in Europe, 19 in Asia, 7 in the Americas, 9 in Africa, and 1 in Oceania. Unfractionated heparin, low-molecular-weight heparin, and vitamin K antagonists were available in almost all countries, but shortages were recorded in 13%, 19%, and 15% of them, respectively. Direct oral anticoagulants were available in approximately three-quarters of the surveyed countries. At least one parenteral medication for heparin-induced thrombocytopenia was available in 57% of countries and a shortage was reported in 9% of these. Shortage of thrombolytics was recorded in 50% of countries. Overall, at least one type of catheter-directed therapy system was approved for use in 77% of countries and available in 23% of surveyed institutions. Our findings revealed notable geographic disparities in the worldwide availability of VTE therapies, the access to which appeared to be limited by economic and geopolitical factors. CONCLUSION: We anticipate that this comprehensive information will play a pivotal role in highlighting the shortcomings of VTE therapies and the lack of homogeneous availability globally.

Thrombin generation, bleeding and hemostasis in humans: Protocol for a scoping review of the literature.

INTRODUCTION: Hemostasis and bleeding are difficult to measure. Thrombin generation assays (TGAs) can measure both procoagulant and anticoagulant contributions to coagulation. TGAs might prove useful for the study of bleeding disorders. There has been much progress in TGA methodology over the past two decades, but its clinical significance is uncertain. We will undertake a scoping review of the literature to synthesize available information on the application of TGAs towards the study of bleeding and hemostasis, TGA methodologies being used and to summarize available literature on associations between TGA parameters, bleeding and hemostatic outcomes. METHODS AND ANALYSIS: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched in collaboration with an information specialist. Title/abstract and full-text screening will be carried out independently and in duplicate; eligible study types will include randomized controlled trials, non-randomized studies, systematic reviews, and case series reporting TGA results and bleeding/hemostatic outcomes among humans. Mapping the information identified will be carried out with results presented using qualitative data analytical techniques. ETHICS AND DISSEMINATION: This scoping review will use published, publicly available information. Research ethics approval will not be required. We will disseminate our findings using conference presentations, peer-reviewed publications, social media, and engagement with knowledge users. This review will outline knowledge gaps concerning TGAs, better delineate its applicability as a clinically relevant assay for bleeding. and seek to identify ongoing barriers to its widespread adoption in clinical research, and eventually, in the clinical setting. TRAIL REGULATIONS: Registration ID with Open Science Framework: osf.io/zp4ge.

Effects of inflammation on thrombosis and outcomes in COVID-19: secondary analysis of the ATTACC/ACTIV-4a trial.

Background: Patients hospitalized for COVID-19 are at high risk of thrombotic complications and organ failure, and often exhibit severe inflammation, which may contribute to hypercoagulability. Objectives: To determine whether patients hospitalized for COVID-19 experience differing frequencies of thrombotic and organ failure complications and derive variable benefits from therapeutic-dose heparin dependent on the extent of systemic inflammation and whether observed benefit from therapeutic-dose anticoagulation varies depending on the degree of systemic inflammation. Methods: We analyzed data from 1346 patients hospitalized for COVID-19 enrolled in the ATTACC and ACTIV-4a platforms who were randomized to therapeutic-dose heparin or usual care for whom levels of C-reactive protein (CRP) were reported at baseline. Results: Increased CRP was associated with worse patient outcomes, including a >98% posterior probability of increased organ support requirement, hospital length of stay, risk of 28-day mortality, and incidence of major thrombotic events or death (patients with CRP 40-100 mg/L or ≥100 mg/L compared to patients with CRP <40 mg/L). Patients with CRP 40 to 100 mg/L experienced the greatest degree of benefit from treatment with therapeutic doses of unfractionated or low molecular weight heparin compared with usual-care prophylactic doses. This was most significant for an increase in organ support-free days (odds ratio: 1.63; 95% confidence interval, 1.09-2.40; 97.9% posterior probability of beneficial effect), with trends toward benefit for other evaluated outcomes. Conclusion: Moderately ill patients hospitalized for COVID-19 with CRP between 40 mg/L and 100 mg/L derived the greatest benefit from treatment with therapeutic-dose heparin.

Neurotrophic keratitis: inflammatory pathogenesis and novel therapies.

PURPOSE OF REVIEW: Neurotrophic keratitis is a rare degenerative disease characterized by decrease or absence of corneal sensation. Neurotrophic keratitis varies from mild forms with mild epitheliopathy to severe manifestations such as corneal ulceration, melting and perforation that can lead to irreversible visual loss. The cause of neurotrophic keratitis comprises a long list of diseases, medications, congenital or genetic conditions as well as trauma. The mechanism of neurotrophic keratitis is complex and multifactorial and its understanding is crucial to better address the treatment strategies. We aimed to review neurotrophic keratitis pathology, mechanisms and management. RECENT FINDINGS: Corneal nerves are critical for the homeostasis of a healthy ocular surface. The lack of nerve-derived neuromediators and corneal-released neuropeptides, neuro-trophins and neurotrophic factors in neurotrophic keratitis leads to a decrease in trophic supply to corneal cells in addition to a decrease in afferent signaling to the brain. This results in pathological tear secretion, decreased blinking rate, corneal healing along with ocular surface and corneal inflammation. Lately, nerve growth factor in special gained emphasis as a treatment strategy targeting the disease mechanism rather than its manifestations. Other therapies, including surgical interventions, are in the pipeline of neurotrophic keratitis management. However, there are still no proper therapeutic guidelines and neurotrophic keratitis treatment remains challenging. SUMMARY: Neurotrophic keratitis may have a devastating outcome and treatment is still challenging. Understanding the disease pathology may assist in the development of new treatment strategies. Prompt disease recognition and immediate intervention are key factors to promote corneal healing and avoid further deterioration.

Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19: a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial.

Background: Acute kidney injury (AKI) in patients with COVID-19 is partly mediated by thromboinflammation. In noncritically ill patients with COVID-19, therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support. Objectives: We investigated whether therapeutic-dose heparin reduces the incidence of AKI or death in noncritically ill patients hospitalized for COVID-19. Methods: We report a prespecified secondary analysis of the ACTIV4a and ATTACC open-label, multiplatform randomized trial of therapeutic-dose heparin vs usual-care pharmacologic thromboprophylaxis on the incidence of severe AKI (≥2-fold increase in serum creatinine or initiation of kidney replacement therapy (KDIGO stage 2 or 3) or all-cause mortality in noncritically ill patients hospitalized for COVID-19. Bayesian statistical models were adjusted for age, sex, D-dimer, enrollment period, country, site, and platform. Results: Among 1922 enrolled, 23 were excluded due to pre-existing end stage kidney disease and 205 were missing baseline or follow-up creatinine measurements. Severe AKI or death occurred in 4.4% participants assigned to therapeutic-dose heparin and 5.5% assigned to thromboprophylaxis (adjusted relative risk [aRR]: 0.72; 95% credible interval (CrI): 0.47, 1.10); the posterior probability of superiority for therapeutic-dose heparin (relative risk < 1.0) was 93.6%. Therapeutic-dose heparin was associated with a 97.7% probability of superiority to reduce the composite of stage 3 AKI or death (3.1% vs 4.6%; aRR: 0.64; 95% CrI: 0.40, 0.99) compared to thromboprophylaxis. Conclusion: Therapeutic-dose heparin was associated with a high probability of superiority to reduce the incidence of in-hospital severe AKI or death in patients hospitalized for COVID-19.

Effect of PCC on Thrombin Generation among Patients on Factor Xa Inhibitors with Major Bleeding or Needing Urgent Surgery (GAUGE): Design and Rationale.

Background Direct factor Xa inhibitors (FXaIs) account for most oral anticoagulant use and FXaI-associated bleeding events are common. Clinicians have variable national and regional access to specific FXaI reversal agents such as andexanet alfa. Many centers have adopted the use of prothrombin complex concentrates (PCCs) as hemostatic therapy for FXaI-associated major bleeding events. PCC does not impact circulating FXaI levels and its mechanism of action to achieve hemostasis in FXaI-associated bleeding is uncertain. While PCC increases quantitative thrombin generation assay (TGA) parameters, it does not correct FXaI-altered thrombin generation kinetics, nor does it normalize thrombin generation. Clinical data supporting the use of PCC are based on cohort studies reporting clinical hemostatic efficacy, which is difficult to measure. The benefits of PCC for FXaI-associated bleeding beyond supportive care are uncertain. Objective GAUGE is a prospective observational study designed to measure the effects of four-factor PCC administration (Octaplex) on TGA parameters among patients with FXaI-associated bleeding or needing urgent surgery. Methods Laboratory outcomes will include the mean paired change in TGA parameters from pre- to post-PCC administration and the proportion of participants whose post-PCC TGA values fall within a defined reference range. Clinical outcomes will include hemostatic efficacy, thromboembolic complications, and all-cause death at 30 days post-PCC. Conclusion Development of a viable and universally accessible FXaI bleed management strategy is crucial. GAUGE will provide in vivo data on the effects of PCC among patients with FXaI-associated bleeding.

Developing a Quality Assurance Framework for Neuro-Ophthalmology Using a Multisite Data Registry.

BACKGROUND: Quality assurance (QA) in neuro-ophthalmology (NOPH) is often lacking. We aimed to assess the quality of referral assessment and time to consult for common neuro-ophthalmological conditions by implementing a quality-assurance registry, NODE (Neuro-ophthalmology Database), in a tertiary neuro-ophthalmology clinic. Australian standardized triage categories, namely, P1 (consult ≤30 days), P2 (consult ≤30-60 days), and P3 (consult ≤60-90 days), were developed and validated for neuro-ophthalmological conditions. METHODS: We collected data from NODE on 676 patients at the Alfred Hospital, Melbourne and developed a consensus on the assignation of NOPH conditions to triage categories using a modified Delphi approach. A panel of 7 experienced neuro-ophthalmologists scored conditions and assignation to triage categories. Consensus was considered when ≥75% of the panel strongly agreed or agreed. We analyzed the mean days from referral to triage and from triage to the initial consultation and compared that with the developed triage category standard. RESULTS: Most patients presenting to the service were female (64%). Common diagnoses were idiopathic intracranial hypertension (IIH) (19%), optic neuropathy (ON) (14%), nonspecific headaches (11%), cranial nerve defects (CND) (8%), and papilledema (7%). Consensus on triage category assignment was reached after 2 rounds of scoring from expert panel members. The mean time from referral to triage was performed in <5 days for all the common diagnosis at the NOPH clinic. The mean days (±SD) from P1 category triage to initial consult for IIH was 15 (±12) days, acute ON 16 (±14) days, CND was 20 (±15) days, and papilledema was 20 (±19) days. The mean days from P2 triage to initial consultant for nonspecific headaches was 22 (±20) days and for EOMD was 48 (±22) days. The mean time (days) from P3 triage to initial consultant for nonocular myasthenia gravis was 38 days (±29) days and for visual snow was 54 (±31) days. CONCLUSIONS: We have established a consensus agreement on triage categories for neuro-ophthalmological conditions, which can be further validated using a larger panel of experts. We established a NOPH registry that will serve as a framework to benchmark quality of care between NOPH services. Data from our NOPH registry demonstrated that most conditions are appropriately triaged and seen.

Pediatric and Adolescent Flatfoot: A Questionnaire Based Middle East and North Africa Study.

Background: Flatfoot is commonly seen in the community and is a common cause of concern for parents because it could become symptomatic and lead to decreased quality of life. One of the most used management approaches is foot orthoses, although no clear evidence supports their use. We aimed to study flatfoot symptoms' prevalence, effect on activities of daily living, and the use and effectiveness of orthoses. Methodology: This was a cross-sectional study that included five countries from the Middle East and North Africa region (Jordan, Palestine, Syria, Egypt, and Iraq). Data were collected using an online questionnaire directed toward parents of children aged 0 to 16 from September to December 2020. The demographic factors were expressed as frequencies (percentages) using standard descriptive statistical parameters, and Pearson's chi-square test was used to examine the relationship between study factors. Results: 1256 participants were recruited using this online survey. The majority (29.6%) of children were diagnosed in the age group of 0 to 2. The abnormal appearance of the foot was the most common (78.7%) complaint. Overall, 54.2% of patients were prescribed orthoses, of which 36.8% noticed improvement in flatness and 37.6% reported relief of symptoms. Conclusion: This study demonstrated that most participants have no or minimal symptoms and that there is a mismatch between participants' expectations and the actual effectiveness of orthoses. Taking into consideration that there is no clear evidence to support the corrective effect of orthoses, we recommend that physicians prescribing them adhere more to their proper indications and spend more time and effort counseling and addressing patients' and parents' concerns about this developmental stage.

Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma In Situ.

NeuVax is a vaccine comprised of the HER2-derived MHC class I peptide E75 (nelipepimut-S, NPS) combined with GM-CSF. We completed a randomized trial of preoperative vaccination with NeuVax versus GM-CSF alone in patients with ductal carcinoma in situ (DCIS). The primary objective was to evaluate for NPS-specific cytotoxic T lymphocyte (CTL) responses. Patients with human leukocyte antigen (HLA)-A2-positive DCIS were enrolled and randomized 2:1 to NeuVax versus GM-CSF alone and received two inoculations prior to surgery. The number of NPS-specific CTL was measured pre-vaccination, at surgery, and 1 and 3 to 6 months post-operation by dextramer assay. Differences in CTL responses between groups and between pre-vaccination and 1-month post-operation were analyzed using a two-sample t test or Wilcoxon rank sum test. The incidence and severity of adverse events were compared between groups. Overall, 45 patients were registered; 20 patients were HLA-A2 negative, 7 declined participation, 1 withdrew, and 4 failed screening for other reasons. The remaining 13 were randomized to NeuVax (n = 9) or GM-CSF alone (n = 4). Vaccination was well-tolerated with similar treatment-related toxicity between groups with the majority (>89%) of adverse events being grade 1. The percentage of NPS-specific CTLs increased in both arms between baseline (pre-vaccination) and 1-month post-operation. The increase was numerically greater in the NPS+GM-CSF arm, but the difference was not statistically significant. NPS+GM-CSF is safe and well-tolerated when given preoperatively to patients with DCIS. In patients with HLA-A2-positive DCIS, two inoculations with NPS+GM-CSF can induce in vivo immunity and a continued antigen-specific T-cell response 1-month postsurgery. PREVENTION RELEVANCE: This trial showed that vaccination of patients with HLA-A2-positive DCIS with NeuVax in the preoperative setting can induce a sustained antigen-specific T-cell response. This provides proof of principle that vaccination in the preoperative or adjuvant setting may stimulate an adaptive immune response that could potentially prevent disease recurrence.

Factors from healthcare delivery affecting breast cancer survival in a health area of Northern of Spain.

OBJECTIVE: Clinical breast cancer decision-making significantly affects life expectancy and management of hospital resources. The aims of the present study were to estimate the time of survival for breast cancer patients and to identify independent factors from healthcare delivery associated with survival rates in a specific health area of Northern of Spain. METHODS: Survival analysis was conducted among a cohort of 2545 patients diagnosed with breast cancer between 2006 and 2012 from the population breast cancer registry of Asturias-Spain and followed up till 2019. Adjusted Cox proportional hazard models were used to identify the independent prognostic factors of all-cause from death. RESULTS: The 5-year survival rate was 80%. Advanced age (>80 years) (hazard ratio, HR: 4.35; 95% confidence interval, CI: 3.41-5.54), hospitalization in small hospitals (HR: 1.46; 95% CI: 1.09-1.97), treatment in oncology wards (HR: 3.57; 95% CI: 2.41-5.27), and length of stay >30 days (HR: 2.24; 95% CI: 1.32-3.79) were the main predictors of death. By contrast, breast cancer suspected via screening was associated with a lower risk of death (HR: 0.55; 95% CI: 0.35-0.87). CONCLUSION: There is room for improvement in survival rates after breast cancer in the health area of Asturias (Northern of Spain). Some healthcare delivery factors, and other clinical characteristics of the tumor influence the survival of breast cancer patients. Strengthening population screening programs could be relevant to increasing survival rates.

Previous Vaccination History and Psychological Factors as Significant Predictors of Willingness to Receive Mpox Vaccination and a Favorable Attitude towards Compulsory Vaccination.

During the ongoing multi-country monkeypox (Mpox) outbreak, healthcare workers (HCWs) have represented a key group in mitigating disease spread. The current study aimed to evaluate the attitude of nurses and physicians in Jordan towards Mpox vaccination, as well as their attitude towards compulsory vaccination against coronavirus disease 2019 (COVID-19), influenza, and Mpox. An online survey was distributed in January 2023 based on the previously validated 5C scale for psychological determinants of vaccination. Previous vaccination behavior was assessed by inquiring about the history of getting the primary and booster COVID-19 vaccination, influenza vaccine uptake during COVID-19, and any history of influenza vaccine uptake. The study sample consisted of 495 respondents: nurses (n = 302, 61.0%) and physicians (n = 193, 39.0%). Four hundred and thirty respondents (86.9%) had heard of Mpox before the study, and formed the final sample considered for Mpox knowledge analysis. Deficiencies in Mpox knowledge were reflected in a mean knowledge score of 13.3 ± 2.7 (out of 20.0 as the maximum score), with significantly lower knowledge among nurses and females. The intention to receive Mpox vaccination was reported by 28.9% of the participants (n = 143), while 33.3% were hesitant (n = 165), and 37.8% were resistant (n = 187). In multivariate analysis, Mpox vaccine acceptance was significantly associated with previous vaccination behavior, reflected in higher vaccine uptake and with higher 5C scores, while Mpox knowledge was not correlated with Mpox vaccination intention. The overall attitude towards compulsory vaccination was neutral, while a favorable attitude towards compulsory vaccination was associated with higher 5C scores and a history of previous vaccination uptake. The current study showed a low intention to get Mpox vaccination in a sample of nurses and physicians practicing in Jordan. The psychological factors and previous vaccination behavior appeared as the most significant determinants of Mpox vaccine acceptance and of attitudes towards compulsory vaccination. The consideration of these factors is central to policies and strategies aiming to promote vaccination among health professionals in efforts to prepare for future infectious disease epidemics.

[Efficacy, effectiveness and safety of the adjuvanted influenza vaccine in the population aged 65 or over]. / Eficacia, efectividad y seguridad de la vacuna antigripal adyuvada en población de 65 o más años de edad.

Most of the complications and deaths related to seasonal flu occur in the elderly population (≥65 years) with comorbidities, and the influenza vaccine is the most effective way to prevent them. Immunization is less effective in older adults due to immunosenescence. MF59-adjuvanted vaccines, designed to improve the magnitude, persistence and amplitude of the immune response in elderly people, have been used in clinical practice since 1997 in their trivalent formulation and, since 2020, in their tetravalent formulation. Data from various studies show that these vaccines are not only safe for all age groups, with a reactogenicity profile similar to that of the conventional vaccine, but also that they are especially effective in boosting the immune response in the population aged 65 or over by increasing antibody titers after vaccination and significantly reducing the risk of hospital admission. Adjuvanted vaccines have been shown to provide cross-protection against heterologous strains and to be as effective as the high-dose vaccine in the population aged 65 or over. In this review, the scientific evidence on the efficacy and effectiveness of the MF59-adjuvanted vaccine in real clinical practice in people ≥65 years of age is analyzed through a narrative and descriptive review of the literature with data from clinical trials, observational studies and systematic reviews or meta-analysis.

Ex vivo demonstration of canine corneal pre-Descemet's anatomy using pneumodissection as for the big bubble technique for deep anterior lamellar keratoplasty.

The recent discovery and characterization of pre-Descemet's layer (PDL; also termed the Dua's layer or the Dua-Fine layer) has advanced the understanding of various posterior corneal pathologies and surgeries in human. This study aimed to characterize the ultrastructure of the posterior stroma and interfacial zone of Descemet's membrane (DM) in canine eyes. Eighteen canine corneo-scleral discs were included. Intrastromal air injection resulted in the formation of type 1 big bubble (BB) in 73% (n = 11/15) of corneas, with a mean diameter of 11.0 ± 1.3 mm. No type 2 BB was created. Anterior segment optical coherence tomography, histology and transmission electron microscopy confirmed that the wall of BB was composed of DM, in contact with remaining stroma (canine PDL; cPDL). The cPDL was populated with keratocytes, of varying thickness of 16.2 ± 4.2 µm in close apposition to the DM, and composed of collagen bundles arranged in transverse, longitudinal and oblique directions. The interfacial zone, between DM and cPDL, showed fibril extension in all three directions, predominantly longitudinal. Irregular extensions of DM material into cPDL stroma were observed. No long-spaced collagen was detected. In conclusion, there exists a well-defined cleavage plane between the posterior stroma and cPDL, with similar but not identical characteristics as in humans, that is revealed by pneumodissection. This adds to our understanding of the anatomy of the posterior most canine cornea, which will have significant clinical impact on posterior corneal surgery and understanding of corneal pathology in dogs.

Efficacy of Alternative Dose Regimens of Exemestane in Postmenopausal Women With Stage 0 to II Estrogen Receptor-Positive Breast Cancer: A Randomized Clinical Trial.

Importance: Successful therapeutic cancer prevention requires definition of the minimal effective dose. Aromatase inhibitors decrease breast cancer incidence in high-risk women, but use in prevention and compliance in adjuvant settings are hampered by adverse events. Objective: To compare the noninferiority percentage change of estradiol in postmenopausal women with estrogen receptor-positive breast cancer given exemestane, 25 mg, 3 times weekly or once weekly vs a standard daily dose with a noninferiority margin of -6%. Design, Setting, and Participants: This multicenter, presurgical, double-blind phase 2b randomized clinical trial evaluated 2 alternative dosing schedules of exemestane. Postmenopausal women with estrogen receptor-positive breast cancer who were candidates for breast surgery were screened from February 1, 2017, to August 31, 2019. Blood samples were collected at baseline and final visit; tissue biomarker changes were assessed from diagnostic biopsy and surgical specimen. Biomarkers were measured in different laboratories between April 2020 and December 2021. Interventions: Exemestane, 25 mg, once daily, 3 times weekly, or once weekly for 4 to 6 weeks before surgery. Main Outcomes and Measures: Serum estradiol concentrations were measured by solid-phase extraction followed by liquid chromatography-tandem mass spectrometry detection. Toxic effects were evaluated using the National Cancer Institute terminology criteria, and Ki-67 was assessed by immunohistochemistry. Results: A total of 180 women were randomized into 1 of the 3 arms; median (IQR) age was 66 (60-71) years, 63 (60-69) years, and 65 (61-70) years in the once-daily, 3-times-weekly, and once-weekly arms, respectively. In the intention-to-treat population (n = 171), the least square mean percentage change of serum estradiol was -89%, -85%, and -60% for exemestane once daily (n = 55), 3 times weekly (n = 56), and once weekly (n = 60), respectively. The difference in estradiol percentage change between the once-daily and 3-times-weekly arms was -3.6% (P for noninferiority = .37), whereas in compliant participants (n = 153), it was 2.0% (97.5% lower confidence limit, -5.6%; P for noninferiority = .02). Among secondary end points, Ki-67 and progesterone receptor were reduced in all arms, with median absolute percentage changes of -7.5%, -5.0%, and -4.0% for Ki-67 in the once-daily, 3-times-weekly, and once-weekly arms, respectively (once daily vs 3 times weekly, P = .31; once daily vs once weekly, P = .06), and -17.0%, -9.0%, and -7.0% for progesterone receptor, respectively. Sex hormone-binding globulin and high-density lipoprotein cholesterol had a better profile among participants in the 3-times-weekly arm compared with once-daily arm. Adverse events were similar in all arms. Conclusions and Relevance: In this randomized clinical trial, exemestane, 25 mg, given 3 times weekly in compliant patients was noninferior to the once-daily dosage in decreasing serum estradiol. This new schedule should be further studied in prevention studies and in women who do not tolerate the daily dose in the adjuvant setting. Trial Registration: ClinicalTrials.gov Identifier: NCT02598557; EudraCT: 2015-005063-16.