Difficulty and help with activities of daily living among older adults living alone during the COVID-19 pandemic: a multi-country population-based study.

BACKGROUND: Older adults who live alone and have difficulties in activities of daily living (ADLs) may have been more vulnerable during the COVID-19 pandemic. However, little is known about pandemic-related changes in ADL assistance (such as home care, domiciliary care) and its international variation. We examined international patterns and changes in provision of ADL assistance, and related these to country-level measures including national income and health service expenditure. METHODS: We analysed data covering 29 countries from three longitudinal cohort studies (Health and Retirement Study, English Longitudinal Study of Aging, and Survey of Health, Ageing and Retirement in Europe). Eligible people were aged ≥50 years and living alone. Outcomes included ADL difficulty status (assessed via six basic ADLs and five instrumental ADLs) and receipt of ADL assistance. Wealth-related inequality and need-related inequity in ADL assistance were measured using Erreygers' corrected concentration index (ECI). Correlations were estimated between prevalence/inequality/inequity in ADL assistance and national health-related indicators. We hypothesized these measures would be associated with health system factors such as affordability and availability of ADL assistance, as well as active ageing awareness. RESULTS: During COVID-19, 18.4% of older adults living alone reported ADL difficulties (ranging from 8.8% in Switzerland to 29.2% in the USA) and 56.8% of those reporting difficulties received ADL assistance (ranging from 38.7% in the UK to 79.8% in Lithuania). Females were more likely to receive ADL assistance than males in 16/29 countries; the sex gap increased further during the pandemic. Wealth-related ECIs indicated socioeconomic equality in ADL assistance within 24/39 countries before the pandemic, and significant favouring of the less wealthy in 18/29 countries during the pandemic. Needs-related ECIs indicated less equity in assistance with ADLs during the pandemic than before. Our hypotheses on the association between ADL provision measures and health system factors were confirmed before COVID-19, but unexpectedly disconfirmed during COVID-19. CONCLUSION: This study revealed an unequal (and in some countries, partly needs-mismatched) response from countries to older adults living alone during the COVID-19 pandemic. The findings might inform future research about, and policies for, older adults living alone, particularly regarding social protection responses during crises.

Adaptive trial designs for spinal cord injury clinical trials directed to the central nervous system.

STUDY DESIGN: Narrative review. PURPOSE: To provide an overview of adaptive trial designs, and describe how adaptive methods can address persistent challenges encountered by randomized controlled trials of people with spinal cord injury (SCI). RESULTS: With few exceptions, adaptive methodologies have not been incorporated into clinical trial designs of people with SCI. Adaptive methods provide an opportunity to address high study costs, slow recruitment, and excessive amount of time needed to carry out the trial. The availability of existing SCI registries are well poised to support modeling and simulation, both of which are used extensively in adaptive trial designs. Eight initiatives for immediate advancement of adaptive methods in SCI were identified. CONCLUSION: Although successfully applied in other fields, adaptive clinical trial designs in SCI clinical trial programs have been narrow in scope and few in number. Immediate application of several adaptive methods offers opportunity to improve efficiency of SCI trials. Concerted effort is needed by all stakeholders to advance adaptive clinical trial design methodology in SCI.

Lower extremity outcome measures: considerations for clinical trials in spinal cord injury.

STUDY DESIGN: This is a focused review article. OBJECTIVES: To identify important concepts in lower extremity (LE) assessment with a focus on locomotor outcomes and provide guidance on how existing outcome measurement tools may be best used to assess experimental therapies in spinal cord injury (SCI). The emphasis lies on LE outcomes in individuals with complete and incomplete SCI in Phase II-III trials. METHODS: This review includes a summary of topics discussed during a workshop focusing on LE function in SCI, conceptual discussion of corresponding outcome measures and additional focused literature review. RESULTS: There are a number of sensitive, accurate, and responsive outcome tools measuring both quantitative and qualitative aspects of LE function. However, in trials with individuals with very acute injuries, a baseline assessment of the primary (or secondary) LE outcome measure is often not feasible. CONCLUSION: There is no single outcome measure to assess all individuals with SCI that can be used to monitor changes in LE function regardless of severity and level of injury. Surrogate markers have to be used to assess LE function in individuals with severe SCI. However, it is generally agreed that a direct measurement of the performance for an appropriate functional activity supersedes any surrogate marker. LE assessments have to be refined so they can be used across all time points after SCI, regardless of the level or severity of spinal injury. SPONSORS: Craig H. Neilsen Foundation, Spinal Cord Outcomes Partnership Endeavor.

Considerations and recommendations for selection and utilization of upper extremity clinical outcome assessments in human spinal cord injury trials.

STUDY DESIGN: This is a focused review article. OBJECTIVES: This review presents important features of clinical outcomes assessments (COAs) in human spinal cord injury research. Considerations for COAs by trial phase and International Classification of Functioning, Disability and Health are presented as well as strengths and recommendations for upper extremity COAs for research. Clinical trial tools and designs to address recruitment challenges are identified. METHODS: The methods include a summary of topics discussed during a two-day workshop, conceptual discussion of upper extremity COAs and additional focused literature review. RESULTS: COAs must be appropriate to trial phase and particularly in mid-late-phase trials, should reflect recovery vs. compensation, as well as being clinically meaningful. The impact and extent of upper vs. lower motoneuron disease should be considered, as this may affect how an individual may respond to a given therapeutic. For trials with broad inclusion criteria, the content of COAs should cover all severities and levels of SCI. Specific measures to assess upper extremity function as well as more comprehensive COAs are under development. In addition to appropriate use of COAs, methods to increase recruitment, such as adaptive trial designs and prognostic modeling to prospectively stratify heterogeneous populations into appropriate cohorts should be considered. CONCLUSIONS: With an increasing number of clinical trials focusing on improving upper extremity function, it is essential to consider a range of factors when choosing a COA. SPONSORS: Craig H. Neilsen Foundation, Spinal Cord Outcomes Partnership Endeavor.

Improving translatability of spinal cord injury research by including age as a demographic variable.

Pre-clinical and clinical spinal cord injury (SCI) studies differ in study design, particularly in the demographic characteristics of the chosen population. In clinical study design, criteria such as such as motor scores, neurological level, and severity of injury are often key determinants for participant inclusion. Further, demographic variables in clinical trials often include individuals from a wide age range and typically include both sexes, albeit historically most cases of SCI occur in males. In contrast, pre-clinical SCI models predominately utilize young adult rodents and typically use only females. While it is often not feasible to power SCI clinical trials to test multi-variable designs such as contrasting different ages, recent pre-clinical findings in SCI animal models have emphasized the importance of considering age as a biological variable prior to human experiments. Emerging pre-clinical data have identified case examples of treatments that diverge in efficacy across different demographic variables and have elucidated several age-dependent effects in SCI. The extent to which these differing or diverging treatment responses manifest clinically can not only complicate statistical findings and trial interpretations but also may be predictive of worse outcomes in select clinical populations. This review highlights recent literature including age as a biological variable in pre-clinical studies and articulates the results with respect to implications for clinical trials. Based on emerging unpredictable treatment outcomes in older rodents, we argue for the importance of including age as a biological variable in pre-clinical animal models prior to clinical testing. We believe that careful analyses of how age interacts with SCI treatments and pathophysiology will help guide clinical trial design and may improve both the safety and outcomes of such important efforts.

Public opinion on sharing data from health services for clinical and research purposes without explicit consent: an anonymous online survey in the UK.

OBJECTIVES: UK National Health Service/Health and Social Care (NHS/HSC) data are variably shared between healthcare organisations for direct care, and increasingly de-identified for research. Few large-scale studies have examined public opinion on sharing, including of mental health (MH) versus physical health (PH) data. We measured data sharing preferences. DESIGN/SETTING/INTERVENTIONS/OUTCOMES: Pre-registered anonymous online survey, measuring expressed preferences, recruiting February to September 2020. Participants were randomised to one of three framing statements regarding MH versus PH data. PARTICIPANTS: Open to all UK residents. Participants numbered 29 275; 40% had experienced an MH condition. RESULTS: Most (76%) supported identifiable data sharing for direct clinical care without explicit consent, but 20% opposed this. Preference for clinical/identifiable sharing decreased with geographical distance and was slightly less for MH than PH data, with small framing effects. Preference for research/de-identified data sharing without explicit consent showed the same small PH/MH and framing effects, plus greater preference for sharing structured data than de-identified free text. There was net support for research sharing to the NHS, academic institutions, and national research charities, net ambivalence about sharing to profit-making companies researching treatments, and net opposition to sharing to other companies (similar to sharing publicly). De-identified linkage to non-health data was generally supported, except to data held by private companies. We report demographic influences on preference. A majority (89%) supported a single NHS mechanism to choose uses of their data. Support for data sharing increased during COVID-19. CONCLUSIONS: Support for healthcare data sharing for direct care without explicit consent is broad but not universal. There is net support for the sharing of de-identified data for research to the NHS, academia, and the charitable sector, but not the commercial sector. A single national NHS-hosted system for patients to control the use of their NHS data for clinical purposes and for research would have broad support. TRIAL REGISTRATION NUMBER: ISRCTN37444142.

Development and Validation of Crosswalks Between FIM® and SCIM III for Voluntary Musculoskeletal Movement Functions.

Background. In spinal cord injury, there are multiple databases containing information on functional recovery, but data cannot be pooled or compared due to differences in how function is measured. A crosswalk is needed to link or convert scores between instruments. Objectives. To create a crosswalk between the voluntary musculoskeletal movement items in the Functional Independence Measure (FIM®) and the Spinal Cord Independence Measure III (SCIM III) for spinal cord injury. Methods. Retrospective datasets with FIM® and SCIM III on the same people were used to develop (Swiss dataset, n = 662) and validate (US, n = 119, and Canadian datasets, n = 133) the crosswalks. Three different crosswalk methods (expert panel, equipercentile, and Rasch analysis) were employed. We used the correlation between observed scores on FIM® and SCIM III to crosswalked scores as the primary criterion to assess the strength of the crosswalk. Secondary criteria such as score distributions, Cohen's effect size, point differences, and subgroup invariance were also evaluated. Results. All three methods resulted in strong correlation coefficients, exceeding the primary criterion value of r = .866 (.897-.972). Assessment of secondary criteria suggests the equipercentile and Rasch methods produced the strongest crosswalks. Conclusions. The Rasch FIM®/SCIM III crosswalk is recommended because it is based on co-calibration of linearized measures, allowing for more sophisticated parametric analyses. The crosswalk will allow comparisons of voluntary musculoskeletal functional recovery across international databases using different functional measures, as well as different systems of care and rehabilitation approaches.

Toward Inclusive Trial Protocols in Heterogeneous Neurological Disorders: Prediction-Based Stratification of Participants With Incomplete Cervical Spinal Cord Injury.

BACKGROUND: Several novel drug- and cell-based potential therapies for spinal cord injury (SCI) have either been applied or will be considered for future clinical trials. Limitations on the number of eligible patients require trials be undertaken in a highly efficient and effective manner. However, this is particularly challenging when people living with incomplete SCI (iSCI) represent a very heterogeneous population in terms of recovery patterns and can improve spontaneously over the first year after injury. OBJECTIVE: The current study addresses 2 requirements for designing SCI trials: first, enrollment of as many eligible participants as possible; second, refined stratification of participants into homogeneous cohorts from a heterogeneous iSCI population. METHODS: This is a retrospective, longitudinal analysis of prospectively collected SCI data from the European Multicenter study about Spinal Cord Injury (EMSCI). We applied conditional inference trees to provide a prediction-based stratification algorithm that could be used to generate decision rules for the appropriate inclusion of iSCI participants to a trial. RESULTS: Based on baseline clinical assessments and a defined subsequent clinical endpoint, conditional inference trees partitioned iSCI participants into more homogeneous groups with regard to the illustrative endpoint, upper extremity motor score. Assuming a continuous endpoint, the conditional inference tree was validated both internally as well as externally, providing stable and generalizable results. CONCLUSION: The application of conditional inference trees is feasible for iSCI participants and provides easily implementable, prediction-based decision rules for inclusion and stratification. This algorithm could be utilized to model various trial endpoints and outcome thresholds.

Sacral sparing in SCI: beyond the S4-S5 and anorectal examination.

BACKGROUND CONTEXT: Sensory and/or motor function sparing, including the S4-S5 spinal cord segment, is central to classifying neurologic impairment after spinal cord injury (SCI) using the American Spinal Injury Association Impairment Scale (AIS) grades within the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Within the ISNCSCI protocol, which is essential for both clinical and research purposes, assessing sacral sparing requires an anorectal and S4-S5 examination. However, in situations where these data are incomplete, the relationships between anorectal/S4-S5 examinations and functional preservation at more rostral sacral segments may be useful. PURPOSE: To evaluate whether slightly more rostral sensory and motor outcomes of the ISNCSCI can accurately predict caudal sacral sparing (S4-S5 dermatome sensation, "deep pressure" anal sensation [AS], and voluntary anal contraction [AC]). STUDY DESIGN: Retrospective analysis of the European Multicenter Study about Spinal Cord Injury database. PATIENT SAMPLE: One thousand four hundred sixty-seven AIS-A, AIS-B, and AIS-C subjects. OUTCOME MEASURES: International Standards for Neurological Classification of Spinal Cord Injury examinations. METHODS: The value of six factors (sensory preservation at S1, S2, and S3; motor preservation at S1; motor function at more than three segments below the motor level; and sensory function at more than three segments below the neurologic level) for predicting ISNCSCI sacral sparing measures (AS, S4-S5 dermatome sensation, AC) was evaluated. Combinations of the most promising factors were then evaluated for their ability to accurately predict the AIS grade. RESULTS: Preserved sensation at the first sacral segment (S1S) provided good prediction (90.5%) of caudal sacral sensory sparing (ie, AS or S4-S5 sensation). Voluntary anal contraction was accurately predicted by preserved motor function within the first sacral segment (S1M) in 85.4% of cases. The alternate classification schemes evaluated for accurately predicting the AIS classification grade were S1S+S1M and S1S+motor preservation more than three segments below the motor level. The ability of these schemes to accurately predict AIS grades was stable over time but varied with the rostrocaudal level of spinal injury. For the initial baseline examination, the alternate classification schemes were accurate in ~95% of cases for T2-T9 SCI, with slightly lower accuracy for cervical SCI (~80%). CONCLUSIONS: There are close relationships between functional sparing at different sacral segments. These relationships can be used to estimate AIS grades when complete information about the anorectal and S4-S5 examination is not available. The accuracy of the classification remains stable over time, while the increased variability in lower levels of SCI, that is, lumbar injuries, emphasizes the importance of careful sacral examinations. The highly reliable predictive values of S1-S3 segments can complement conclusions from anorectal examinations if the latter are considered to be confounded or incomplete.

Traumatic thoracic ASIA A examinations and potential for clinical trials.

STUDY DESIGN: Retrospective review of prospective database. OBJECTIVE: To define the variability of neurologic examination and recovery after nonpenetrating complete thoracic spinal cord injuries (American Spinal Injury Association [ASIA] A). SUMMARY OF BACKGROUND DATA: Neurologic examinations after spinal cord injury (SCI) can be difficult and inconsistent. Unlike cervical SCI patients, alterations in thoracic (below T1) complete SCI (ASIA A-based on the ASIA Impairment Scale [AIS]) patients' examinations are based only on sensory testing, thus changes in the neurologic level (NL) are determined only by sensory changes. METHODS: A retrospective review of the placebo control patients in a multicenter prospective database used for the pharmacologic trial of Sygen. Patients were included if they had a complete thoracic SCI on initial evaluation, with completed ASIA examinations at follow-up weeks 4, 8, 16, 26, and 52. Specifically, pin prick (PP) and light touch (LT) were assessed and the absolute change was calculated as the number of spinal levels at a given observation time. RESULTS: Three thousand one hundred sixty-five patients were initially screened for the Sygen clinical trial, of which 51 were the control placebo patients used in this analysis. Alterations from the baseline examination (PP and LT) were fairly consistent and the median change/recovery in neurologic examination was 1 spinal level. Across all observations postbaseline, the average change for PP was 1.48 +/- 0.13 (mean +/- SE), and for LT, 1.40 +/- 0.13. There were equal proportions of directional changes (none, improved, lost). CONCLUSION: Changes in a thoracic complete (ASIA A) SCI patients ASIA examination as measured through sensory methods (PP/LT) are fairly uncommon. The overall examination had only 1- to 2-level variability across patients, indicating minimal change in the sensory examination over the follow-up period. Stability in the ASIA examination as measured through sensory methods has thus been demonstrated over time, making it an excellent tool to monitor changes in neurologic function.