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. 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% received education at the time of VTE diagnosis only, leading to 63.5% receiving no 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 about the quality of education received. While overall consistent, findings in selected survey domains appeared to numerically differ across age group, ethnicity, continent of residence, educational level, metastatic status, and VTE history. CONCLUSION: 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.

Health-related quality of life following valoctocogene roxaparvovec gene therapy for severe hemophilia A in the phase 3 trial GENEr8-1.

BACKGROUND: Severe hemophilia A (HA) negatively impacts health-related quality of life (HRQOL). OBJECTIVES: We aimed to analyze HRQOL in adult men with severe HA without inhibitors after valoctocogene roxaparvovec gene transfer in the phase 3 trial GENEr8-1. METHODS: Participant-reported outcomes were the hemophilia-specific quality of life questionnaire for adults (Haemo-QOL-A), the EQ-5D-5L instrument, the Hemophilia Activities List (HAL), and the Work Productivity and Activity Impairment Questionnaire: Hemophilia Specific (WPAI+CIQ:HS). Participants completed the questionnaires at baseline and through 104 weeks postinfusion with 6 × 1013 vg/kg of valoctocogene roxaparvovec. Scores were analyzed per participant characteristics and outcomes. RESULTS: For 132 HIV-negative participants, mean change from baseline in Haemo-QOL-A Total Score met the anchor-based clinically important difference (CID: 5.5) by week 12; the mean (SD) increase was 7.0 (12.6) at week 104. At week 104, improvement in Consequences of Bleeding, Treatment Concern, Worry, and Role Functioning domain scores exceeded the CID (6). EQ-5D-5L Utility Index scores improved above the CID at week 52, but not at week 104. EQ-5D-5L visual analog scale and HAL scores increased from baseline to week 104. Participants reported less activity and work impairment at week 104 than baseline. Participants with problem joints had lower mean baseline Haemo-QOL-A Total and domain scores than those without them, but improved over 104 weeks, except for 11 participants with ≥3 problem joints. Participants with 0 bleeds during the baseline prophylaxis period reported Haemo-QOL-A score improvements above the CID, including in the Consequences of Bleeding domain. CONCLUSION: Valoctocogene roxaparvovec provided clinically meaningful HRQOL improvement for men with severe HA.

The clinicopathological features of thrombosis with thrombocytopenia syndrome following ChAdOx1-S (AZD1222) vaccination and case outcomes in Australia: a population-based study.

Background: Thrombosis with thrombocytopenia syndrome (TTS) associated with viral vector COVID-19 vaccines, including ChAdOx1-S (AstraZeneca AZD1222) vaccine, can result in significant morbidity and mortality. We report the clinicopathological features of TTS following ChAdOx1-S vaccination and summarise the case outcomes in Australia. Methods: In this cohort study, patients diagnosed with TTS in Australia between 23 March and 31 December 2021 were identified according to predefined criteria. Cases were included if they met the Therapeutic Goods Administration (TGA) probable and confirmed case definitions and were reclassified using Centres for Disease Control and Prevention (CDC) definition for analysis. Data were collected on patient baseline characteristics, clinicopathological features, risk factors, treatment and outcomes. Findings: A total of 170 TTS cases were identified, with most occurring after the first dose (87%) of ChAdOx1-S. The median time to symptom onset after vaccination and symptom onset to admission was 11 and 2 days respectively. The median age of cases was 66 years (interquartile range 55-74). All except two patients received therapeutic anticoagulation and 66% received intravenous immunoglobulin. Overall, 85.3% of cases were discharged home after a median hospitalisation of 6 days, 9.4% required ongoing rehabilitation and 5.3% died. Eight deaths were related to TTS, with another dying from an unrelated condition while receiving treatment for TTS. Deaths occurred more commonly in those classified as Tier 1 according to the CDC definition and were associated with more severe thrombocytopenia and disease-related haemorrhage. Interpretation: TTS, while rare, can be severe and have catastrophic outcomes in some individuals. In Australia, the mortality rate was low compared to that reported in other high-income countries. Almost all received therapeutic anticoagulation with no bleeding complications and were successfully discharged. This emphasises the importance of community education and an established pathway for early recognition, diagnosis and treatment of TTS. Funding: Australian Commonwealth Department of Health and Aged Care. H.A Tran, N. Wood, J. Buttery, N.W. Crawford, S.D. Chunilal, V.M. Chen are supported by Medical Research Future Funds (MRFF) grant ID 2015305.

Immune thrombocytopenia and COVID-19 vaccination: Outcomes and comparisons to prepandemic patients.

Background: Immune thrombocytopenia (ITP) has been reported following COVID-19 vaccination. After index case fatalities, there was concern among patients both with and without a prior history of ITP in Australia. Objectives: To describe treatment outcomes of ITP after COVID-19 vaccination and compare relapsed vs historical pre-COVID-19 ITP cohorts. Methods: We collected ITP cases in Australia within 6 weeks of receiving any COVID-19 vaccination as part of primary vaccination (up to October 17, 2021). Second, we reviewed platelet charts in a historical ITP cohort to determine whether platelet variability was distinct from relapsed ITP after vaccination. Results: We report on 50 patients (37 de novo, 13 relapsed ITP) vaccinated from March 22, 2021, to October 17, 2021. Although there was 1 fatality, bleeding was otherwise mostly minor: (70% WHO bleeding grade <2). De novo ITP was more likely after AstraZeneca ChAdOx1 nCoV-19 (89%) than Pfizer BNT162b2 (11%). Most patients responded quickly (median, 4 days; complete response, 40 of 45 [89%]). In the historical cohort, only 6 of 47 patients exhibited platelet variability (>50% decrease and platelets <100 × 109/L), but median platelet nadir was significantly higher than vaccination relapse (27 vs 6 × 109/L, P =.005). Conclusion: ITP was more frequently reported after AstraZeneca ChAdOx1 nCoV-19 than Pfizer BNT162b2 vaccination. Standard ITP treatments remain highly effective for de novo and relapsed ITP (96%). Although thrombocytopenia can be severe after vaccination, bleeding is usually mild. Despite some sampling bias, our data do not support a change in treatment strategies for patients with ITP after vaccination.

Understanding work experience in epidemic-induced telecommuting: The roles of misfit, reactance, and collaborative technologies.

In the management of the global COVID-19 pandemic, the mandated closure of workplaces and stay-at-home orders have forced workers to adapt to a prolonged period of unplanned telecommuting, which we term epidemic-induced telecommuting. Although epidemic-induced telecommuting has drastically altered how work is conducted, scant attention is being paid to this emerging work arrangement. To this end, we combine psychological reactance theory and person-environment fit theory to advance the concept of misfit between worker and environment as a core determinant of employees' work experience in the epidemic-induced telecommuting. Particularly, we distinguish between supply-value and demand-ability misfits as constraints on workers' freedom at work. Having analyzed data collected through a survey administered on remote workers, we discovered that both misfits positively influenced workers' perceived psychological reactance, which led to work exhaustion and counter-productive behaviors. We also found that the utilization of collaborative technologies moderated the effects of misfit on workers' psychological reactance.

The Balance Recovery Confidence (BRC) Scale.

BACKGROUND: Falls efficacy posits an understanding of the perceived ability to prevent and manage falls. There have been no validated self-reported instruments to measure the perceived ability to recover balance in response to destabilizing perturbations. PURPOSE: To develop a scale of balance recovery confidence. METHODS: Stage one had candidate items generated by 12 community-dwelling adults aged 65 and older using the nominal group technique. Stage two had the scale's name, instructions, response options, recall period and the items validated for appropriateness with 28 healthcare professionals and 10 older adults using an e-Delphi technique. Stage three had the scale's psychometric properties evaluated with 84 older adults who had completed self-reported and performance measures. Factor analysis was applied to confirm unidimensionality. The internal structure, reliability and validity of the scale were evaluated using the classical test theory and Rasch measurement theory. RESULTS: The 19-item scale was developed and validated with experts' consensus. The scale is unidimensional with excellent internal structure (Cronbach's α = 0.975) and test-retest reliability with Intraclass Correlation Coefficient (ICC3,1) = 0.944. Construct validity of the scale was supported by its relationships with the other measures (Activities-specific Balance Confidence scale, Falls Efficacy Scale-International, Late-Life Function and Disability International-Function, handgrip strength dynamometry, 30-second chair stand test, and mini-BESTest). CONCLUSION: The balance recovery confidence scale is a distinct instrument that measures perceived reactive balance recovery. The scale has good psychometric properties and can be used to complement other measurement instruments to help older adults cope with challenges to balance.

Awareness of venous thromboembolism among patients with cancer: Preliminary findings from a global initiative for World Thrombosis Day.

BACKGROUND: Cancer-associated venous thromboembolism (CAT) has detrimental impact on patients' clinical outcomes and quality of life. Data on CAT education, communication, and awareness among the general cancer population are scanty. METHODS: We present the preliminary results of an ongoing patient-centered survey including 27 items covering major spheres of CAT. The survey, available in 14 languages, was promoted and disseminated online through social networks, email newsletters, websites, and media. RESULTS: As of September 20, 2022, 749 participants from 27 countries completed the survey. Overall, 61.8% (n = 460) of responders were not aware of their risk of CAT. Among those who received information on CAT, 26.2% (n = 56) were informed only at the time of CAT diagnosis. Over two thirds (69.1%, n = 501) of participants received no education on signs and symptoms of venous thromboembolism (VTE); among those who were educated about the possible clinical manifestations, 58.9% (n = 119) were given instructions to seek consultation in case of VTE suspicion. Two hundred twenty-four respondents (30.9%) had a chance to discuss the potential use of primary thromboprophylaxis with health-care providers. Just over half (58.7%, n = 309) were unaware of the risks of bleeding associated with anticoagulation, despite being involved in anticoagulant-related discussions or exposed to anticoagulants. Most responders (85%, n = 612) valued receiving CAT education as highly relevant; however, 51.7% (n = 375) expressed concerns about insufficient time spent and clarity of education received. CONCLUSIONS: This ongoing survey involving cancer patients with diverse ethnic, cultural, and geographical backgrounds highlights important patient knowledge gaps. These findings warrant urgent interventions to improve education and awareness, and reduce CAT burden.

Treatment of immune thrombocytopenia in Australian adults: A multicenter retrospective observational study.

Background: In Australia, prescribing restrictions limit access to internationally recommended second-line therapies such as rituximab and thrombopoietin agonists (TPO-A) (eltrombopag and romiplostim). Subsequent lines of therapy include an array of immunosuppressive and immune-modulating agents directed by drug availability and physician and patient preference. Objectives: The objective of the study was to describe the use of first and subsequent lines of treatment for adult immune thrombocytopenia (ITP) in Australia and to assess their effectiveness and tolerability. Patients/Methods: A retrospective review of medical records was conducted of 322 patients treated for ITP at eight participating centers in Australia between 2013 and 2020. Data were analyzed by descriptive statistics and frequency distribution using pivot tables, and comparisons between centers were assessed using paired t tests. Results: Mean age at diagnosis of ITP was 48.8 years (standard deviation [SD], 22.6) and 58.3% were women. Primary ITP was observed in 72% and secondary ITP in 28% of the patients; 95% of patients received first-line treatment with prednisolone (76%), dexamethasone (15%), or intravenous immunoglobulin (48%) alone or in combination. Individuals with secondary ITP were less steroid dependent (72% vs. 76%) and required less treatment with a second-line agent (47% vs. 58%) in the study sample. Over half (56%) of the cohort received treatment with one or more second-line agents. The mean number of second-line agents used for each patient was 1.9 (SD, 1.2). The most used second-line therapy was rituximab, followed by etrombopag and splenectomy. These also generated the highest rates of complete response (60.3%, 72.1%, and 71.8% respectively). The most unfavorable side effect profiles were seen in long-term corticosteroids and splenectomy. Conclusion: A wide range of "second-line" agents were used across centers with variable response rates and side effect profiles. Findings suggest greater effectiveness of rituximab and TPO-A, supporting their use earlier in the treatment course of patients with ITP across Australia.

Assessment of immunological anti-platelet factor 4 antibodies for vaccine-induced thrombotic thrombocytopenia (VITT) in a large Australian cohort: A multicenter study comprising 1284 patients.

BACKGROUND: Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus-based vaccines aimed to prevent and minimize COVID-19 and related pathophysiology. OBJECTIVES: To describe patterns of testing for anti-platelet factor 4 (PF4) antibodies using various ELISA assays in a large Australian cohort and comparative functional platelet activation assays in a subset. PATIENTS/METHODS: Asserachrom HPIA IgG ELISA was performed in 1284 patients over a period of 12 months, supplemented in select cohorts by comparative ELISA using three other methods (n = 78-179), three different functional assays (flow cytometry, serotonin release assay, and/or Multiplate; n = 476), and rapid immunological chemiluminescence anti-PF4 assay (n = 460), in a multicenter study. RESULTS: For first episode presentations, 190/1284 (14.8%) ELISA tests were positive. Conversely, most (445/460; 96.7%) chemiluminescence anti-PF4 test results were negative. All functional assays showed associations of higher median ELISA optical density with functional positivity and with high rates of ELISA positivity (64.0% to 85.2%). Data also identified functional positivity in 14.8%-36.0% of ELISA negative samples, suggesting false negative VITT by HPIA IgG ELISA in upward of one third of assessable cases. CONCLUSION: To our knowledge, this is the largest multicenter evaluation of anti-PF4 testing for investigation of VITT. Discrepancies in test results (ELISA vs. ELISA or ELISA vs. functional assay) in some patients highlighted limitations in relying on single methods (ELISA and functional) for PF4 antibody detection in VITT, and also highlights the variability in phenotypic test presentation and pathomechanism of VITT.

Interventions and measurement instruments used for falls efficacy in community-dwelling older adults: A systematic review.

Falls efficacy has been defined as perceived self-belief in the prevention and management of falls. In the case of community-dwelling older adults, it is essential that interventions should address the different aspects of falls efficacy in terms of balance confidence, balance recovery confidence, safe landing confidence and post-fall recovery confidence to improve their agency to deal with falls. This review aims to provide the current landscape of falls efficacy interventions and measurement instruments. A literature search of five electronic databases was conducted to extract relevant trials from January 2010 to September 2021, and the CASP tool for critical appraisal was applied to assess the quality and applicability of the studies. Eligibility criteria included randomised controlled trials evaluating falls efficacy as a primary or secondary outcome for community-dwelling older adults. A total of 302 full texts were reviewed, with 47 selected for inclusion involving 7,259 participants across 14 countries. A total of 63 interventions were identified, using exercise and other components to target different aspects of falls efficacy. The novel contribution of this article is to highlight that those interventions were applied to address the different fall-related self-efficacies across pre-fall, near-fall, fall landing and completed fall stages. Appropriate measurement instruments need to be used to support empirical evidence of clinical effectiveness.

Consensus guidelines for the management of adult immune thrombocytopenia in Australia and New Zealand.

INTRODUCTION: The absence of high quality evidence for basic clinical dilemmas in immune thrombocytopenic purpura (ITP) underlines the need for contemporary guidelines relevant to the local treatment context. ITP is diagnosed by exclusions, with a hallmark laboratory finding of isolated thrombocytopenia. MAIN RECOMMENDATIONS: Bleeding, family and medication histories and a review of historical investigations are required to gauge the bleeding risk and possible hereditary syndromes. Beyond the platelet count, the decision to treat is affected by individual bleeding risk, disease stage, side effects of treatment, concomitant medications, and patient preference. Treatment is aimed at achieving a platelet count > 20 × 109 /L, and avoidance of severe bleeding. Steroids are the standard first line treatment, with either 6-week courses of tapering prednisone or repeated courses of high dose dexamethasone providing equivalent efficacy. Intravenous immunoglobulin can be used periprocedurally or as first line therapy in combination with steroids. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: There is no consensus on choice of second line treatments. Options with the most robust evidence include splenectomy, rituximab and thrombopoietin receptor agonists. Other therapies include azathioprine, mycophenolate mofetil, dapsone and vinca alkaloids. Given that up to one-third of patients achieve a satisfactory haemostatic response, splenectomy should be delayed for at least 12 months if possible. In life-threatening bleeding, we recommend platelet transfusions to achieve haemostasis, along with intravenous immunoglobulin and high dose steroids.

Falls efficacy: Extending the understanding of self-efficacy in older adults towards managing falls.

Falls efficacy is a widely studied construct. The understanding of falls efficacy has evolved over time. Falls efficacy was initially perceived to be suitably used as a measure of fear of falling. However, further research suggested that falls efficacy and fear of falling are distinct constructs, and therefore, would be inappropriate to be used as a proxy. Instead, some researchers posited that falls efficacy is synonymous with balance confidence. Falls efficacy has been conventionally understood as the perceived ability of individuals to perform activities without losing balance or falling. A recently conducted systematic review by the authors on existing falls efficacy related measures had revealed a fresh perspective of recognising falls efficacy as a perceived ability to manage a threat of a fall. Falls efficacy, with a broadened interpreted construct, relates to the individual's perceived self-efficacy of performing necessary actions needed in different scenarios, including pre-fall, near-fall, fall-landing and completed fall. The conventional interpretation of falls efficacy needs a rethinking of perspective. An extended understanding of falls efficacy would provide an integral approach towards improving the agency of individual to deal with falls and would enhance person-centred care.

Falls efficacy instruments for community-dwelling older adults: a COSMIN-based systematic review.

BACKGROUND: Falls efficacy is a widely-studied latent construct in community-dwelling older adults. Various self-reported instruments have been used to measure falls efficacy. In order to be informed of the choice of the best measurement instrument for a specific purpose, empirical evidence of the development and measurement properties of falls efficacy related instruments is needed. METHODS: The Consensus-based Standards for the Selection of Health Measurement Intruments (COSMIN) checklist was used to summarise evidence on the development, content validity, and structural validity of instruments measuring falls efficacy in community-dwelling older adults. Databases including MEDLINE, Web of Science, PsychINFO, SCOPUS, CINAHL were searched (May 2019). Records on the development of instruments and studies assessing content validity or structural validity of falls efficacy related scales were included. COSMIN methodology was used to guide the review of eligible studies and in the assessment of their methodological quality. Evidence of content validity: relevance, comprehensiveness and comprehensibility and unidimensionality for structural validity were synthesised. A modified GRADE approach was applied to evidence synthesis. RESULTS: Thirty-five studies, of which 18 instruments had been identified, were included in the review. High-quality evidence showed that the Modified Falls Efficacy Scale (FES)-13 items (MFES-13) has sufficient relevance, yet insufficient comprehensiveness for measuring falls efficacy. Moderate quality evidence supported that the FES-10 has sufficient relevance, and MFES-14 has sufficient comprehensibility. Activities-specific Balance Confidence (ABC) Scale-Simplified (ABC-15) has sufficient relevance in measuring balance confidence supported by moderate-quality evidence. Low to very low-quality evidence underpinned the content validity of other instruments. High-quality evidence supported sufficient unidimensionality for eight instruments (FES-10, MFES-14, ABC-6, ABC-15, ABC-16, Iconographical FES (Icon-FES), FES-International (FES-I) and Perceived Ability to Prevent and Manage Fall Risks (PAPMFR)). CONCLUSION: Content validity of instruments to measure falls efficacy is understudied. Structural validity is sufficient for a number of widely-used instruments. Measuring balance confidence is a subset of falls efficacy. Further work is needed to investigate a broader construct for falls efficacy.

Near-falls in Singapore community-dwelling older adults: a feasibility study.

BACKGROUND: A near-fall is defined as a loss of balance that would result in a fall if sufficient balance recovery manoeuvres are not executed. Compared to falls, near-falls and its associated balance recovery manoeuvres have been understudied. Older adults may not recognise a near-fall or identify the use of their balance recovery manoeuvres to prevent a fall. The consensus on the methods to collect near-fall data is lacking. The primary objective of this study was to determine the feasibility of recruitment and retention. Secondary objectives were to establish evidence that Singapore community-dwelling older adults can identify near-falls and associated balance recovery manoeuvres. Texting and calling methods were explored as reporting methods. METHODS: This study took place in Singapore (September to October 2019). Participants were healthy, community-dwelling adults aged 65 or older. Recruitment was done through poster advertisement, and all participants gave informed consent. Participants attended a briefing session and reported their near-fall or fall incidence over 21 days using either daily texting or calling. The primary outcome measures were the recruitment rate, retention rate, preferred modes for data reporting and ability to report near-falls or falls. Secondary outcomes included the self-reported incidence of falls and near-falls. RESULTS: Thirty older adults were recruited in 5 weeks. All participants completed the study. They understood near-fall concepts and were able to report the occurrence and relevant balance recovery manoeuvres used to prevent a fall. 87% (26/30) chose to text while 13% (4/30) selected calling as their reporting method. One actual fall (0.16%) out of 630 responses was reported. Thirty-six incidents (5.7%) of near-falls were recorded. Sixteen participants (53.3%) experienced near-falls and half of this group experienced two or more near-falls. The use of reach-to-grasp strategy (36%), compensatory stepping (52.8%), and other body regions (11.2%) were used to prevent the fall. CONCLUSIONS: The study provided evidence that studying near-falls in Singapore community-dwelling older adults is feasible and can be applied to a large-scale study. Recruitment and retention rates were good. Older adults were able to identify near-falls and balance recovery manoeuvres. Both texting and calling were feasible reporting methods, but texting was preferred. TRIAL REGISTRATION: ClinicalTrials identifier: NCT04087551 . Registered on September 12, 2019.

A multicentre assessment of contemporary laboratory assays for heparin induced thrombocytopenia.

Heparin induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy. In some patients, HIT causes platelet activation and thrombosis (sometimes abbreviated HITT), which leads to adverse clinical sequalae ('pathological HIT'). The likelihood of HIT is initially assessed clinically, typically using a scoring system, of which the 4T score is that most utilised. Subsequent laboratory testing to confirm or exclude HIT facilitates exclusion or diagnosis and management. The current investigation comprises a multicentre (n=9) assessment of contemporary laboratory testing for HIT, as performed over the past 1-3 years in each site and comprising testing of over 1200 samples. The primary laboratory test used by study participants (n=8) comprised a chemiluminescence procedure (HIT-IgG(PF4-H)) performed on an AcuStar instrument. Additional immunological testing performed by study sites included lateral flow (STiC, Stago), enzyme linked immunosorbent assay (ELISA), Asserachrom (HPIA IgG), PaGIA (BioRad), plus functional assays, primarily serotonin release assay (SRA) or platelet aggregation methods. The chemiluminescence procedure yielded a highly sensitive screening method for identifying functional HIT, given high area under the curve (AUC, generally ≥0.9) in a receiver operator characteristic (ROC) analysis against SRA as gold standard. ELISA testing resulted in lower ROC AUC scores (<0.8) and higher levels of false positives. Although there is clear association with the likelihood of HIT, the 4T score had less utility than literature suggests, and was comparable to a previous study reported by some of the authors.