Normative reference values, determinants and regression equations for the incremental shuttle walk test (ISWT) in healthy Asian population aged 21 to 80 years.

BACKGROUND: The validated Incremental Shuttle Walk Test (ISWT) is widely used for evaluating maximal exercise capacity, with the distance-walked (IWSD) as the primary outcome. However, there are no normative reference values (NRV) and reference equations to predict ISWD for the Singaporean population. OBJECTIVES: This study aims to establish the NRV and reference equations for ISWD in healthy Singaporeans aged 21 to 80 and investigate the determining variables during ISWT. METHODS: This cross-sectional study recruited community-dwelling healthy subjects aged 21-80 from the community via convenience sampling. Each subject completed two trials of the ISWT according to the standard protocol. Variables measured during the trials included ISWD, pre-and post-test heart rate (HR), oxygen saturation, blood pressure (BP), modified Borg's dyspnoea score and Borg's rate of perceived exertion (RPE). RESULTS: 199 healthy Singaporean (females = 114, males = 85) participated in the study. The overall median ISWD was 660.0 metres (m) [interquartile range (IQR):440.0-850.0]. The age-stratified mean ISWD ranged from 430.0 m (IQR:350.0-450.0) (aged 60-80) to 480.0 m (IQR:438.0-650.0) (aged 40-59) to 780.0 m (IQR:670.0-960.0) (aged 21-39). Gender, age, weight, height and HR change (highest post-test HR minus pre-test HR) were the most significant variables (p < 0.001). IWSD (m) = 651.4(Height, m) +89.7(Gender, male = 1; female = 0) -6.31(Age, years) -3.61(Weight, kilograms) +2.54(HR change, beats per minute); R2 = 0.741. Previously published ISWT reference equations cannot accurately predict the ISWD in the Singaporean population. CONCLUSIONS: This study investigated the ISWD NRV and established reference equations for healthy Singaporeans aged 21-80. The information would be beneficial in setting performance benchmarks to guide physical assessment, intervention and rehabilitation.

Antibody drug conjugates for the treatment of multiple myeloma.

The treatment landscape of multiple myeloma (MM) has evolved substantially, but it remains largely incurable so new treatment options are required. Antibody drug conjugates (ADCs) are an emerging therapeutic class used in Cancer to deliver targeted therapy. ADCs are composed of three components, an antibody, a chemical linker and a payload which must be chosen carefully to be effective and safe. This alternative mechanism of action to standard treatments makes ADCs an attractive class for further development. However, several ADCs have been investigated but many have not moved further than phase 1 trials, highlighting the challenges in designing an effective and tolerable ADC. Belantamab Mafodotin is currently the only ADC licensed for MM although others are currently under evaluation. Belantamab Mafodotin demonstrated efficacy as monotherapy in triple class exposed patients and combinations are under development which maintain safety with encouraging efficacy particularly at earlier lines of therapy. Retaining an acceptable adverse event profile for ADCs remains vital for their success. Strategies to mitigate ocular events for Belantamab Mafodotin involve lower and less frequent dosing as well as the use of gamma secretase inhibitors. The optimal sequencing of ADCs within the treatment pathway including novel immunotherapies is now under evaluation.

Effect of the COVID-19 pandemic on individuals with spinal cord injury: Mental health and use of telehealth.

INTRODUCTION: Limited access to health care services and the self-isolation measures due to the coronavirus disease 2019 (COVID-19) pandemic may have had additional unintended negative effects, affecting the health of individuals with spinal cord injury (SCI). OBJECTIVES: To examine the perceived influence of the COVID-19 pandemic on individuals with SCI. First, this study looked to understand how the pandemic affected the use and perception of telehealth services for these individuals. Second, it investigated the effect of COVID-19 on mental health. DESIGN: Cross-sectional online survey. SETTING: Individuals with SCI living in the community in British Columbia, Canada. PATIENTS: This survey was offered to individuals with SCI and had 71 respondents, with 34% living in a rural setting and 66% in an urban setting. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Telehealth utility, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7 (GAD-7), Fear of COVID-19 scale (FCV-19S), and Perceived Vulnerability to Disease (PVD). RESULTS: Telehealth use in the SCI population has increased from 9.9% to 25.4% over the pandemic, with rates of telehealth use in urban centers nearing those of rural participants. Thirty-one percent of respondents had probable depression and 7.0% had probable generalized anxiety disorder as measured by a score of ≥10 on the PHQ-9 and GAD-7, respectively. The mean scores on FCV-19S and PVD were 17.0 (6.6 SD) and 4.29 (1.02 SD), respectively. CONCLUSION: Telehealth use during COVID-19 has more than doubled. It is generally well regarded by respondents, although only a fourth of the SCI population has reported its use. With this in mind, it is important to understand the barriers to further adoption. In addition, higher rates of probable depression were seen than those estimated by pre-pandemic studies in other countries.

Perspectives from the spinal cord injury community with teleSCI services during the COVID-19 pandemic: a qualitative study.

PURPOSE: To explore individuals with spinal cord injury (SCI) experiences with and perceptions towards teleSCI services during the COVID-19 global pandemic in British Columbia, Canada. METHOD: Using maximum variation sampling, we invited selected individuals from a larger quantitative dataset (n = 71) to partake in an interview. In total, 12 individuals participated in the study. Interviews were recorded and transcribed verbatim. Interview transcripts were then coded and analysed by team members using qualitative descriptive analysis. RESULTS: Individuals with an SCI perceived teleSCI services to be convenient, accessible, affordable, and an effective way to access some healthcare services during the COVID-19 pandemic. However, in-person healthcare was still needed by many participants to effectively manage and treat their SCI-associated secondary conditions. CONCLUSION: Our findings suggest that, in a post-pandemic world, the SCI community would benefit from blended models of healthcare delivery that leverage telecommunication technologies to increase accessibility to healthcare while still providing in-person care for assessments and treatments.Implications for RehabilitationIndividuals with an SCI perceived teleSCI services to be convenient, accessible, affordable, and an effective way to access some healthcare services during the COVID-19 pandemic. However, in-person healthcare was still needed and desired by those with an SCI to effectively manage and treat their SCI-associated secondary conditions.In a post-pandemic world, individuals with an SCI would benefit from blended models of healthcare delivery that leverage telecommunication technologies to increase accessibility to healthcare, while still providing in-person care for those requiring ongoing treatment and management of secondary conditions associated with the patient's SCI.TeleSCI services offer the potential to allow healthcare professionals and SCI specialists to collaborate (digitally) with patients at the same time. This patient-centered approach could not only help healthcare professionals strategize effective remedies to better manage secondary conditions associated with SCI but could result in overall better-quality care received by those within the SCI community.

Strengthening Australia's Chemical Regulation.

Humans are exposed to a myriad of chemicals every day, some of which have been established to have deleterious effects on human health. Regulatory frameworks play a vital role in safeguarding human health through the management of chemicals and their risks. For this review, we focused on agricultural and veterinary (Agvet) chemicals and industrial chemicals, which are regulated, respectively, by the Australian Pesticides and Veterinary Medicines Authority (APVMA), and the Australian Industrial Chemicals Introduction Scheme (AICIS). The current frameworks have been considered fragmented, inefficient, and most importantly, unsafe in prioritizing human health. We evaluated these frameworks, identified gaps, and suggested improvements that would help bring chemical regulation in Australia in line with comparative regulations in the EU, US, and Canada. Several weaknesses in the Australian frameworks include the lack of a national program to monitor chemical residues, slow pace in conducting chemical reviews, inconsistent risk management across states and territories, a paucity of research efforts on human health impacts, and inadequate framework assessment systems. Recommendations for Australia include establishing a national surveillance and chemical residue monitoring system, harmonizing risk assessment and management across jurisdictions, improving chemical review efficiency, and developing regular performance review mechanisms to ensure that human health is protected.

Vascular-Cognitive Impairment following High-Thoracic Spinal Cord Injury Is Associated with Structural and Functional Maladaptations in Cerebrovasculature.

Individuals living with chronic spinal cord injury (SCI) often exhibit impairments in cognitive function, which impede their rehabilitation and transition into the community. Although a number of clinical studies have demonstrated the impact of impaired cardiovascular control on cognitive impairment, the mechanistic understanding of this deleterious relationship is still lacking. The present study investigates whether chronic disruption of cardiovascular control following experimental SCI results in cerebrovascular decline and vascular cognitive impairment. Fourteen weeks following a high thoracic SCI (at the third thoracic segment), rats were subjected to a battery of in vivo and in vitro physiological assessments, cognitive-behavioral tests, and immunohistochemical approaches to investigate changes in cerebrovascular structure and function in the middle cerebral artery (MCA). We show that in the MCA of rats with SCI, there is a 55% (SCI vs. control: 13.4 ± 1.9% vs. 29.63 ± 2.8%, respectively) reduction in the maximal vasodilator response to carbachol, which is associated with reduced expression of endothelial marker cluster of differentiation 31 (CD31) and transient receptor potential cation channel 4 (TRPV 4) channels. Compared with controls, MCAs in rats with SCI were found to have 50% (SCI vs. control: 1.5 ± 0.2 vs. 1 ± 0.1 a.u., respectively) more collagen 1 in the media of vascular wall and 37% (SCI vs. control: 30.5 ± 2.9% vs. 42.0 ± 4.0%, respectively) less distensibility at physiological intraluminal pressure. Further, the cerebral blood flow (CBF) in the hippocampus was reduced by 32% in the SCI group (SCI vs. control: 44.3 ± 4.5 mL/100 g/min vs. 65.0 ± 7.2 mL/100 g/min, respectively) in association with impairment of short-term memory based on a novel object recognition test. There were no changes in the sympathetic innervation of the vasculature and passive structure in the SCI group. Chronic experimental SCI is associated with structural alterations and endothelial dysfunction in cerebral arteries that likely contribute to significantly reduced CBF and vascular cognitive impairment.

Treatment of classical Hodgkin lymphoma in young adults aged 18-30 years with a modified paediatric Hodgkin lymphoma protocol. Results of a multicentre phase II clinical trial (CRUK/08/012).

This phase II trial was designed to determine the safety and efficacy of a modified paediatric risk-stratified protocol in young adults (18-30 years) with classical Hodgkin Lymphoma. The primary end-point was neurotoxicity rate. The incidence of grade 3 neurotoxicity was 11% (80% CI, 5-19%); a true rate of neuropathy of >15% cannot be excluded. Neuropathy and associated deterioration in quality of life was largely reversible. The overall response rate was 100% with 40% complete remission (CR) rate. Twelve months disease-free survival (DFS) was 91%. We demonstrate that a risk-stratified paediatric combined modality treatment approach can be delivered to young adults without significant irreversible neuropathy.