Attitudes towards COVID-19 vaccination in adults with haematological malignancies.

INTRODUCTION: Despite people with haematological malignancies being particularly vulnerable to severe COVID-19 infection and complications, vaccine hesitancy may be a barrier to optimal vaccination. This study explored attitudes towards COVID-19 vaccination in people with haematological malignancies. METHODS: People with haematological malignancies at nine Australian health services were surveyed between June and October, 2021. Sociodemographic and clinical characteristics were collected. Attitudes towards COVID-19 vaccination were explored using the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale, and the Disease Influenced Vaccine Acceptance Scale-Six. Open-ended comments were qualitatively analysed. RESULTS: A total of 869 people with haematological malignancies (mean age 64.2 years, 43.6% female) participated. Most participants (85.3%) reported that they had received at least one COVID-19 vaccine dose. Participants who were younger, spoke English as a non-dominant language, and had a shorter time since diagnosis were less likely to be vaccinated. Those who were female or spoke English as their non-dominant language reported greater vaccine side-effects concerns. Younger participants reported greater concerns about the vaccine impacting their treatment. CONCLUSION: People with haematological malignancies reported high vaccine uptake, however, targeted education for specific participant groups may address vaccine hesitancy concerns, given the need for COVID-19 vaccine boosters.

Long-term outcomes of corticosteroid graft versus host disease prophylaxis in peripheral blood allogeneic haemopoietic stem cell transplant: a comparative cohort analysis.

BACKGROUND: Corticosteroids (CSs) have previously been incorporated into graft versus host disease (GVHD) prophylaxis regimens for bone marrow (BM) and haemopoietic stem cell transplant (HSCT). AIMS: To assess the impact of prophylactic CS in HSCT using peripheral blood (PB) stem cells. METHODS: Patients were identified from three HSCT centres receiving a first PB-HSCT between January 2011 and December 2015 from a fully human leukocyte antigen (HLA)-matched sibling or unrelated donor for acute myeloid leukaemia or acute lymphoblastic leukaemia. To enable meaningful comparison, patients were divided into two cohorts. RESULTS: Cohort 1 included only myeloablative-matched sibling HSCT, where the only variation in GVHD prophylaxis was the addition of CS. In these 48 patients, there were no differences in GVHD, relapse, non-relapse mortality, overall survival or GVHD-relapse-free-survival (GRFS) at 4 years after transplant. Cohort 2 included the remaining HSCT recipients, where one group received CS-prophylaxis and the non-CS group received an antimetabolite, ciclosporin and anti-T-lymphocyte globulin. In these 147 patients, those receiving CS-prophylaxis experienced higher rates of chronic GVHD (71% vs 18.1%, P < 0.001) and lower rates of relapse (14.9% vs 33.9%, P = 0.02). Those receiving CS-prophylaxis had a lower 4-year GRFS (15.7% vs 40.3%, P = 0.002). CONCLUSIONS: There does not appear to be a role for adding CS to standard GVHD prophylaxis regimens in PB-HSCT.

Serious Underlying Medical Conditions and COVID-19 Vaccine Hesitancy: A Large Cross-Sectional Analysis from Australia.

As COVID-19 vaccinations became available and were proven effective in preventing serious infection, uptake amongst individuals varied, including in medically vulnerable populations. This cross-sectional multi-site study examined vaccine uptake, hesitancy, and explanatory factors amongst people with serious and/or chronic health conditions, including the impact of underlying disease on attitudes to vaccination. A 42-item survey was distributed to people with cancer, diabetes, or multiple sclerosis across ten Australian health services from 30 June to 5 October 2021. The survey evaluated sociodemographic and disease-related characteristics and incorporated three validated scales measuring vaccine hesitancy and vaccine-related beliefs generally and specific to their disease: the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale and the Disease Influenced Vaccine Acceptance Scale-Six. Among 4683 participants (2548 [54.4%] female, 2108 [45.0%] male, 27 [0.6%] other; mean [SD] age, 60.6 [13.3] years; 3560 [76.0%] cancer, 842 [18.0%] diabetes, and 281 [6.0%] multiple sclerosis), 3813 (81.5%) self-reported having at least one COVID-19 vaccine. Unvaccinated status was associated with younger age, female sex, lower education and income, English as a second language, and residence in regional areas. Unvaccinated participants were more likely to report greater vaccine hesitancy and more negative perceptions toward vaccines. Disease-related vaccine concerns were associated with unvaccinated status and hesitancy, including greater complacency about COVID-19 infection, and concerns relating to vaccine efficacy and impact on their disease and/or treatment. This highlights the need to develop targeted strategies and education about COVID-19 vaccination to support medically vulnerable populations and health professionals.

Management and Outcomes of Diffuse Large B-cell Lymphoma Post-transplant Lymphoproliferative Disorder in the Era of PET and Rituximab: A Multicenter Study From the Australasian Lymphoma Alliance.

There are limited data on post-transplant lymphoproliferative disorder (PTLD) in the era of positron emission tomography (PET) and rituximab (R). Furthermore, there is limited data on the risk of graft rejection with modern practices in reduction in immunosuppression (RIS). We studied 91 patients with monomorphic diffuse large B-cell lymphoma PTLD at 11 Australian centers: median age 52 years, diagnosed between 2004 and 2017, median follow-up 4.7 years (range, 0.5-14.5 y). RIS occurred in 88% of patients. For patients initially treated with R-monotherapy, 45% achieved complete remission, rising to 71% with the addition of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP) for those not in complete remission. For patients initially treated with R-CHOP, the complete remission rate was 76%. There was no difference in overall survival (OS) between R-monotherapy and R-chemotherapy patients. There was no difference in OS for patients with systemic lymphoma (n = 68) versus central nervous system (CNS) involvement (n = 23) (3-y OS 72% versus 73%; P = 0.78). Treatment-related mortality was 7%. End of treatment PET was prognostic for patients with systemic lymphoma with longer OS in the PET negative group (3-y OS 91% versus 57%; P = 0.01). Graft rejection occurred in 9% (n = 4 biopsy-proven; n = 4 suspected) during the entire follow-up period with no cases of graft loss. RIS and R-based treatments are safe and effective with a low likelihood of graft rejection and high cure rate for patients achieving complete remission with CNS or systemic PTLD.

Chromosome microarray characterisation of chromosome arm 12p loss associated with complex molecular karyotype and recurrent adverse cytogenetic markers in multiple myeloma.

Copy number loss within chromosome 12 short arm (12p) has gained attention as an adverse cytogenetic marker in multiple myeloma. The prognostic significance and characterisation of the common minimal deleted region remains controversial between various studies with loss of CD27 proposed as the putative critical gene. We aimed to determine the frequency of 12p loss, its correlation with adverse cytogenetic markers further to define and characterise 12p deletions. Our study included a prospective cohort of 574 multiple myeloma patients referred for cytogenetic testing, including interphase fluorescence in situ hybridisation for IGH (14q32.33) translocations and chromosome microarray. Loss of 12p was detected in 54/574 (9.4%) patients and when compared with the non-12p loss group [520/574 (90.6%)], 12p loss patients demonstrated a statistically significant association with specific recurrent cytogenetic markers: complex molecular karyotypes (98.1% vs 45.2%), 1p loss (50.0% vs 20.2%), t(4;14) (20.4% vs 7.7%), 8p loss (37.0% vs 15.0%), 13/13q loss (70.4% vs 41.7%), and 17p loss (33.3% vs 6.5%). The size and location of 12p losses were heterogeneous with a common 0.88 Mb minimally deleted region that included ~9 genes from ETV6 to CDKN1B in 52/54 (~96.3%) patients but did not include CD27. Our findings support 12p loss being a secondary chromosome abnormality frequently co-occurring with adverse cytogenetic markers and complex molecular karyotypes indicative of chromosome instability.

Immune-Mediated Thrombotic Thrombocytopenic Purpura: A Narrative Review of Diagnosis and Treatment in Adults.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and potentially lethal disease characterized by fragmentary hemolysis, moderate-to-severe thrombocytopenia, end-organ dysfunction, and severely reduced ADAMTS13 levels (< 10%). Survival in iTTP has improved significantly since the introduction of plasma exchange as standard therapy combined with immune suppression to address the underlying pathophysiology. A host of challenges remain including prompt recognition of the disease, treatment of the end-organ effects of the disease, improving the early mortality rate, significantly reducing the relapse rate as well as addressing refractory disease. Discussed in this narrative review of iTTP are the recent measures aimed at addressing these issues, including improvements in clinical prediction models, postremission maintenance approaches with early retreatment as well as the development of novel therapies.

Coagulation studies: achieving the right mix in a large laboratory network.

Basic coagulation tests, activated partial thromboplastin time (APTT), prothrombin time (PT) and the related international normalised ratio (INR), are performed frequently in hospital settings. From a laboratory perspective, unexpected abnormal results require further action; either informing the ordering clinician, or second line testing to determine the underlying cause. To streamline laboratory workflow, a new system of expert laboratory rules was implemented. The medical implications of this new laboratory system are evaluated here. The electronic ordering system was updated to mandate clinical information regarding the presence of an anticoagulant, or 'no anticoagulant'. When the PT or APTT were abnormal, and no anticoagulant was reported, second line testing was automatically performed. The second line tests performed were: mixing studies, fibrinogen and thrombin time. Any sample with a mixing study that did not completely correct, or fibrinogen <1.0 g/L, or INR >7.0, was flagged for clinical review by the laboratory haematology registrar. In a 17-month period there were 362,692 APTT, PT/INR and fibrinogen tests performed. Of these, 14,160 (3.9%) were abnormal with either no reported anticoagulant, or an unknown anticoagulant status. A total of 934 (0.3%) were referred for review by the haematology registrar. Three (<0.001%) cases received altered medical management as a result of the haematology registrar review. In hospital settings, most abnormal coagulation studies are anticipated by the ordering clinician. Unexpected abnormal coagulation results of clinical significance are rare. Automated second line coagulation testing and medical review improves laboratory workflow without compromising patient safety.

Reporting of harms by randomised controlled trials in ophthalmology.

To evaluate the reporting of harms by randomised controlled trials investigating intravitreal therapies for diabetic macular oedema. A thorough literature search identified eligible reports. Two authors independently extracted data from these articles using a prospectively created checklist. The main outcome measure was compliance with the 10 recommendations of the 2004 Consolidated Standards of Reporting Trials statement extension for better harms reporting. Secondary outcomes were the predictors of the number of recommendations met and the amount of space devoted to harms reporting. Thirty-six reports involving 7246 eyes met the criteria for analysis. The fidelity of the data extraction was excellent, with Cohen's κ coefficient of 0.90 for all items extracted. The median number of recommendations met was six, IQR 5-7. Recommendation 4 (describe how harms-related information was collected) was met by 97% of articles and recommendation 8 (present the absolute risk of each adverse event) by 92%. The least frequently met recommendations were numbers 3 (list addressed adverse events with definitions of each), 31%, and 6 (describe participant withdrawals because of harms), 36%. The mean percentage of the results section devoted to harms-related data was 25.8%, SD 10.8%. Harms reporting in published reports of trials of intravitreal therapies for diabetic macular oedema is still not entirely adequate despite increased attention and efforts to standardise it.

Distribution of pathology in frontal variant Alzheimer's disease.

Atypical presentations of Alzheimer's disease (AD) have been described, including a "frontal" variant (fvAD), which presents with personality change and executive dysfunction similar to that seen in behavioral variant frontotemporal dementia (bvFTD). This clinical variation is thought to reflect the regional distribution of pathology, although few reports include autopsy confirmation. We compared three clinicopathological groups matched for age at diagnosis and disease duration; those with possible bvFTD who at autopsy had only AD (fvAD), those with typical AD clinically and pathologically, and those with typical clinical bvFTD confirmed pathologically. The density of neurons and AD-type pathology was quantified in the frontal association, occipital association, and entorhinal cortices and hippocampal CA1 regions. Immunohistochemistry for phosphorylated tau and amyloid-ß deposition was used to detect neurofibrillary tangles and plaques. Of the six core clinical features of the International Consensus Criteria, disinhibition, stereotyped behaviors, and executive dysfunction were most common, occurring in five of the six fvAD patients. Other features were rare. While there was no significant difference in neuron density between groups for any of the four regions, when the ratio of frontal:occipital pathology was examined, neuronal density in fvAD was significantly less than AD but similar to bvFTD. The frontal:occipital ratio of AD-type pathology was also greater in fvAD than AD. The findings of this study suggest a frontal variant of AD exists with features that mimic bvFTD and that this reflects a differential distribution of neurodegeneration with more marked pathology in the frontal cortex compared with the occipital cortex.

Dialectical behaviour therapy in an Irish community mental health setting.

OBJECTIVES: Dialectical behaviour therapy (DBT) is a recommended treatment of patients with borderline personality disorder, yet there are few descriptions of the approach in public community mental health settings where the majority of such patients present. This study describes the development and evaluation of a DBT programme in an Irish setting. METHODS: The DBT programme was run over a six month period. Participants were assessed at baseline and post intervention with the following instruments: The Structured Clinical Interview for DSM III R personality disorders (SCID II), the clinical Outcomes in Routine Evaluation (CORE) and the symptom checklist 90 Revised (SCL-90-Revised). Inpatient bed usage was determined from case note review. RESULTS: Outcome data was available for eight subjects. Significant improvement (p < 0.005) was seen on all CORE subscales. SCL-90-R showed significant improvement (p < 0.05) on the global severity index and on the positive symptom distress index. A decrease in self harming behaviour was found. Subjects' inpatient bed days dropped from a mean of 58 in the year pre intervention to a mean of four days in the year post intervention. A novel finding was that 43% of subjects who originally fulfilled criteria for avoidant personality disorder no longer did so post intervention. CONCLUSIONS: The study found that DBT can be applied in a community mental health setting with benefits similar to more specialist settings. Significant difficulties were encountered in implementing the programme. The clinical implications are that specialist psychotherapy services need to be an integral part of psychiatric services to achieve better outcomes for patients with borderline personality disorder.

Bipolar affective disorder associated with 11q24.2 disruption--a second report.

A recent report identified bipolar affective disorder in a patient with a de novo deletion 11q24.2. We record a further instance involving this cytogenetic region and bipolar affective disorder in a patient with a balanced translocation.