Identifying combinations of long-term conditions associated with sarcopenia: a cross-sectional decision tree analysis in the UK Biobank study.

OBJECTIVES: This study aims to determine whether machine learning can identify specific combinations of long-term conditions (LTC) associated with increased sarcopenia risk and hence address an important evidence gap-people with multiple LTC (MLTC) have increased risk of sarcopenia but it has not yet been established whether this is driven by specific combinations of LTC. DESIGN: Decision trees were used to identify combinations of LTC associated with increased sarcopenia risk. Participants were classified as being at risk of sarcopenia based on maximum grip strength of <32 kg for men and <19 kg for women. The combinations identified were triangulated with logistic regression. SETTING: UK Biobank. PARTICIPANTS: UK Biobank participants with MLTC (two or more LTC) at baseline. RESULTS: Of 140 001 participants with MLTC (55.3% women, median age 61 years), 21.0% were at risk of sarcopenia. Decision trees identified several LTC combinations associated with an increased risk of sarcopenia. These included drug/alcohol misuse and osteoarthritis, and connective tissue disease and osteoporosis in men, which showed the relative excess risk of interaction of 3.91 (95% CI 1.71 to 7.51) and 2.27 (95% CI 0.02 to 5.91), respectively, in age-adjusted models. CONCLUSION: Knowledge of LTC combinations associated with increased sarcopenia risk could aid the identification of individuals for targeted interventions, recruitment of participants to sarcopenia studies and contribute to the understanding of the aetiology of sarcopenia.

Rising to the challenge of defining and operationalising multimorbidity in a UK hospital setting: the ADMISSION research collaborative.

PURPOSE: Greater transparency and consistency when defining multimorbidity in different settings is needed. We aimed to: (1) adapt published principles that can guide the selection of long-term conditions for inclusion in research studies of multimorbidity in hospitals; (2) apply these principles and identify a list of long-term conditions; (3) operationalise this list by mapping it to International Classification of Diseases 10th revision (ICD-10) codes. METHODS: Review by independent assessors and ratification by an interdisciplinary programme management group. RESULTS: Agreement was reached that when defining multimorbidity in hospitals for research purposes all conditions must meet the following four criteria: (1) medical diagnosis; (2) typically present for ≥ 12 months; (3) at least one of currently active; permanent in effect; requiring current treatment, care or therapy; requiring surveillance; remitting-relapsing and requiring ongoing treatment or care, and; (4) lead to at least one of: significantly increased risk of death; significantly reduced quality of life; frailty or physical disability; significantly worsened mental health; significantly increased treatment burden (indicated by an increased risk of hospital admission or increased length of hospital stay). Application of these principles to two existing lists of conditions led to the selection of 60 conditions that can be used when defining multimorbidity for research focused on hospitalised patients. ICD-10 codes were identified for each of these conditions to ensure consistency in their operationalisation. CONCLUSIONS: This work contributes to achieving the goal of greater transparency and consistency in the approach to the study of multimorbidity, with a specific focus on the UK hospital setting.

Determining the feasibility of characterising cellular senescence in human skeletal muscle and exploring associations with muscle morphology and physical function at different ages: findings from the MASS_Lifecourse Study.

Cellular senescence may be associated with morphological changes in skeletal muscle and changes in physical function with age although there have been few human studies. We aimed to determine the feasibility of characterising cellular senescence in skeletal muscle and explored sex-specific associations between markers of cellular senescence, muscle morphology, and physical function in participants from the MASS_Lifecourse Study. Senescence markers (p16, TAF (Telomere-Associated DNA Damage Foci), HMGB1 (High Mobility Group Box 1), and Lamin B1) and morphological characteristics (fibre size, number, fibrosis, and centrally nucleated fibres) were assessed in muscle biopsies from 40 men and women (age range 47-84) using spatially-resolved methods (immunohistochemistry, immunofluorescence, and RNA and fluorescence in situ hybridisation). The associations between senescence, morphology, and physical function (muscle strength, mass, and physical performance) at different ages were explored. We found that most senescence markers and morphological characteristics were weakly associated with age in men but more strongly, although non-significantly, associated with age in women. Associations between senescence markers, morphology, and physical function were also stronger in women for HMGB1 and grip strength (r = 0.52); TAF, BMI, and muscle mass (r > 0.4); Lamin B1 and fibrosis (r = - 0.5); fibre size and muscle mass (r ≥ 0.4); and gait speed (r = - 0.5). However, these associations were non-significant. In conclusion, we have demonstrated that it is feasible to characterise cellular senescence in human skeletal muscle and to explore associations with morphology and physical function in women and men of different ages. The findings require replication in larger studies.

Attitudes and barriers to resistance exercise training for older adults living with multiple long-term conditions, frailty, and a recent deterioration in health: qualitative findings from the Lifestyle in Later Life - Older People's Medicine (LiLL-OPM) study.

BACKGROUND: Many older adults live with the combination of multiple long-term conditions (MLTC) and frailty and are at increased risk of a deterioration in health requiring interaction with healthcare services. Low skeletal muscle strength is observed in individuals living with MLTC and is central to physical frailty. Resistance exercise (RE) is the best available treatment for improving muscle strength, but little is known about the attitudes and barriers to RE in this group of older adults. This study therefore aimed to explore the knowledge of and attitudes towards RE, as well as the barriers and enabling factors, in older adults living with MLTC, frailty and a recent deterioration in health. METHODS: Fourteen participants aged 69-92 years (10 women) from the Lifestyle in Later Life - Older People's Medicine (LiLL-OPM) study were recruited from an Older People's Medicine Day Unit in Newcastle, UK. Participants were invited to take part in a semi-structured interview exploring their knowledge and attitudes as well as barriers and enabling factors to RE. Data were analysed using thematic analysis. RESULTS: The analysis generated three themes (1) a lack of awareness and understanding of RE, (2) a self-perceived inability to perform RE; physical and psychological barriers and (3) willingness to perform RE under expert guidance. There was a general lack of awareness and understanding of RE, with most participants having never heard of the term and being unaware of its potential benefits. When RE was described, participants stated that they would be willing to try RE, but it was apparent that an individualised approach underpinned by expert guidance would be required to support engagement. CONCLUSIONS: Older adults living with MLTC, frailty and a recent deterioration in health lack awareness and understanding of RE. Despite a range of barriers, this group appear willing to engage in RE if they are appropriately supported. There is a need to co-design and deliver effective strategies, including education, to raise awareness and understanding of RE, as well as promote engagement in RE, in this group of older adults.

Feasibility of engaging older adults living with multiple long-term conditions, frailty, and a recent deterioration in health in a study of lifestyle: protocol for the LiLL-OPM study.

Community-dwelling older adults living with multiple long-term conditions (MLTC), frailty and a recent deterioration in health are underserved by research. This results in a limited evidence base for their care, including the potential benefits of lifestyle interventions such as structured exercise. The aims of the LiLL-OPM (Lifestyle in Later Life - Older People's Medicine) study are to determine if it is feasible to carry out a research project with these patients, describe their health and lifestyle, their attitudes to engaging in exercise and their experiences of taking part in the research. Older adults who are attending an Older People's Medicine Day Unit service in Newcastle, UK, and their informal carers will be invited to take part. The study will use mixed methods with semi-structured interviews and a health and lifestyle questionnaire, carried out in a way that is most convenient to participants, including in their own homes and with a flexible schedule of study visits. The findings from the feasibility study will provide invaluable data on how to design research, including the most suitable approaches to recruitment and data collection. This will improve the inclusion in research of older adults living with MLTC, frailty and a recent deterioration in health.

Simple approaches to characterising multiple long-term conditions (multimorbidity) and rates of emergency hospital admission: Findings from 495,465 UK Biobank participants.

BACKGROUND: Numerous approaches are used to characterise multiple long-term conditions (MLTC), including counts and indices. Few studies have compared approaches within the same dataset. We aimed to characterise MLTC using simple approaches, and compare their prevalence estimates of MLTC and associations with emergency hospital admission in the UK Biobank. METHODS: We used baseline data from 495,465 participants (age 38-73 years) to characterise MLTC using four approaches: Charlson index (CI), Byles index (BI), count of 43 conditions (CC) and count of body systems affected (BC). We defined MLTC as more than two conditions using CI, BI and CC, and more than two body systems using BC. We categorised scores (incorporating weightings for the indices) from each approach as 0, 1, 2 and 3+. We used linked hospital episode statistics and performed survival analyses to test associations with an endpoint of emergency hospital admission or death over 5 years. RESULTS: The prevalence of MLTC was 44% (BC), 33% (CC), 6% (BI) and 2% (CI). Higher scores using all approaches were associated with greater outcome rates independent of sex and age group. For example, using CC, compared with score 0, score 2 had 1.95 (95% CI: 1.91, 1.99) and a score of 3+ had 3.12 (95% CI: 3.06, 3.18) times greater outcome rates. The discriminant value of all approaches was modest (C-statistics 0.60-0.63). CONCLUSIONS: The counts classified a greater proportion as having MLTC than the indices, highlighting that prevalence estimates of MLTC vary depending on the approach. All approaches had strong statistical associations with emergency hospital admission but a modest ability to identify individuals at risk.

Milk intake across adulthood and muscle strength decline from mid- to late life: the MRC National Survey of Health and Development.

Milk is a source of several nutrients which may be beneficial for skeletal muscle. Evidence that links lower milk intake with declines in muscle strength from midlife to old age is lacking. We used data from the Medical Research Council National Survey of Health and Development to test sex-specific associations between milk consumption from age 36 to 60-64 years, low grip strength (GS) or probable sarcopenia, and GS decline from age 53 to 69 years. We included 1340 men and 1383 women with at least one measure of both milk intake and GS. Milk intake was recorded in 5-d food diaries (aged 36, 43, 53 and 60-64 years), and grand mean of total, reduced-fat and full-fat milk each categorised in thirds (T1 (lowest) to T3 (highest), g/d). GS was assessed at ages 53, 60-64, and 69 years, and probable sarcopenia classified at the age of 69 years. We employed logistic regression to examine the odds of probable sarcopenia and multilevel models to investigate decline in GS in relation to milk intake thirds. Compared with T1, only T2 (58·76-145·25 g/d) of reduced-fat milk was associated with lower odds of sex-specific low GS at the age of 69 years (OR (95 % CI): 0·59 (0·37, 0·94), P = 0·03). In multilevel models, only T3 of total milk (≥ 237·52 g/d) was associated with stronger GS in midlife in men (ß (95 % CI) = 1·82 (0·18, 3·45) kg, P = 0·03) compared with T1 (≤ 152·0 g/d), but not with GS decline over time. A higher milk intake across adulthood may promote muscle strength in midlife in men. Its role in muscle health in late life needs further examination.

Long-term conditions, multimorbidity, lifestyle factors and change in grip strength over 9 years of follow-up: Findings from 44,315 UK biobank participants.

BACKGROUND: Weak grip strength is associated with a range of adverse health outcomes and an accelerated decline in grip strength confers an even greater risk. The factors associated with change in grip strength in mid-life remain to be fully determined. METHODS: We used data from 44,315 UK Biobank participants who had grip strength measured at baseline (2006-10) and a subsequent visit approximately nine years later. At baseline, participants' long-term conditions (LTCs) were categorised against a hierarchy, with multimorbidity characterised by the number of LTC categories. Lifestyle factors were assessed. Change in grip strength was grouped into four patterns: decline, stable low, stable high or reference (no change or increase) and used as the outcome in multinomial logistic regression. RESULTS: Most LTC categories were associated with adverse patterns of change in grip strength (stable low and/or decline): for example, musculoskeletal/trauma conditions were associated with an increased risk of the stable low pattern (Relative Risk Ratio [RRR] = 1.63; 95% confidence interval [CI]: 1.49-1.79). Multimorbidity and lifestyle factors had independent associations with grip strength change. Those with 3+ categories of LTCs were more likely to experience decline in grip strength (RRR = 1.18; 95% CI: 1.08-1.28) compared to those with none. Low physical activity was associated with adverse patterns of grip strength, while raised body mass index (BMI) had divergent associations. CONCLUSIONS: Individuals living with multimorbidity and those with lifestyle risk factors such as low physical activity are at increased risk of low muscle strength and the loss of strength over time.

Correlation of ISO 16840-2:2007 impact damping and hysteresis measures for a sample of wheelchair seating cushions.

Hysteresis and impact damping measures were made on 37 wheelchair seating cushions according to ISO 16840-2:2007 Wheelchair seating-Part 2: Determination of physical and mechanical characteristics of devices intended to manage tissue integrity-seat cushions. These measures were then correlated using Spearman and Pearson correlations to investigate the relationship between them. Correlations were also conducted on the subset of cushions comprising only those with planar foam construction. Correlation between the hysteresis measures (h250 and h500) and the mean number of rebounds greater in amplitude than 10% of the peak acceleration amplitude (R10%) were weak, as were the correlations between the hysteresis measures and the mean peak first rebound acceleration (aa). Correlations between hysteresis and the mean peak second rebound acceleration (a2), and also hysteresis and the ratio of first and second peak (a2:aa) however were moderate. Results demonstrate that the relationship between these two measures is complex. The assertion implicit in ISO 16840-2:2007 is that the two measures are related, but this study shows that these should not be assumed to be equivalent or used interchangeably.

A quantitative measurement method for comparison of seated postures.

This technical note proposes a method to measure and compare seated postures. The three-dimensional locations of palpable anatomical landmarks corresponding to the anterior superior iliac spines, clavicular notch, head, shoulders and knees are measured in terms of x, y and z co-ordinates in the reference system of the measuring apparatus. These co-ordinates are then transformed onto a body-based axis system which allows comparison within-subject. The method was tested on eleven unimpaired adult participants and the resulting data used to calculate a Least Significant Difference (LSD) for the measure, which is used to determine whether two postures are significantly different from one another. The method was found to be sensitive to the four following standardised static postural perturbations: posterior pelvic tilt, pelvic obliquity, pelvic rotation, and abduction of the thighs. The resulting data could be used as an outcome measure for the postural alignment aspect of seating interventions in wheelchairs.

ISO 16840-2:2007 load deflection and hysteresis measurements for a sample of wheelchair seating cushions.

Load deflection and hysteresis measurements were made on 37 wheelchair seating cushions according to ISO 16840-2:2007. Load deflection plots for all 37 cushions are reported and fundamental aspects of graph interpretation discussed. ISO hysteresis data are also reported and interpretation discussed.

K-12 Neuroscience Education Outreach Program: Interactive Activities for Educating Students about Neuroscience.

The University of New England's Center for Excellence in the Neurosciences has developed a successful and growing K-12 outreach program that incorporates undergraduate and graduate/professional students. The program has several goals, including raising awareness about fundamental issues in neuroscience, supplementing science education in area schools and enhancing undergraduate and graduate/professional students' academic knowledge and skill set. The outreach curriculum is centered on core neuroscience themes including: Brain Safety, Neuroanatomy, Drugs of Abuse and Addiction, Neurological and Psychiatric Disorders, and Cognition and Brain Function. For each theme, lesson plans were developed based upon interactive, small-group activities. Additionally, we've organized our themes in a "Grow-up, Grow-out" approach. Grow-up refers to returning to a common theme, increasing in complexity as we revisit students from early elementary through high school. Grow-out refers to integrating other scientific fields into our lessons, such as the chemistry of addiction, the physics of brain injury and neuronal imaging. One of the more successful components of our program is our innovative team-based model of curriculum design. By creating a team of undergraduate, graduate/professional students and faculty, we create a unique multi-level mentoring opportunity that appears to be successful in enhancing undergraduate students' skills and knowledge. Preliminary assessments suggest that undergraduates believe they are enhancing their content knowledge and professional skills through our program. Additionally, we're having a significant, short-term impact on K-12 interest in science. Overall, our program appears to be enhancing the academic experience of our undergraduates and exciting K-12 students about the brain and science in general.

Can static interface pressure mapping be used to rank pressure-redistributing cushions for active wheelchair users?

Interface pressure mapping (IPM) is a clinical tool that assists the selection of seat cushions for pressure management for wheelchair users. Clinical pressure measurements are almost always made under static sitting conditions, although this does not consider the time-dependent properties of some cushion materials that may behave differently under the dynamic conditions of self-propulsion. This study investigated the potential for such differences by collecting seat IPM measurements from eight wheelchair users using four different seat cushion designs during static sitting and self-propulsion. Mean pressure corresponding to the approximate anatomical location of the ischial tuberosities was used to rank the four cushions under the two conditions. The two sets of rankings for each participant were then compared using correlation. Dynamic data from four participants was judged too inconsistent to be interpreted reliably and demonstrates the practical difficulties associated with dynamic IPM measurement when variations in individual propulsion technique cannot be controlled. Strong correlations were observed between rank orders for the remaining four participants and suggest that the statically derived pressure measures can be used for clinical decision making when selecting cushions for self-propelling wheelchair users.

Repeatability of a new observational gait score for unilateral lower limb amputees.

The aim of this study was to assess the repeatability of an observational gait analysis score that was developed specifically for unilateral amputees. Ten videotaped sequences were analysed by six experienced observers on two separate occasions. Data were analysed using percentage agreement, the kappa statistic and the coefficient of repeatability. The score demonstrated good intraobserver repeatability with an average repeatability coefficient of 3 (range 1.5-4.6). Interobserver repeatability was poor with a repeatability coefficient of 5.9. This score could be used in practice to assess amputees and is most repeatable if used by the same observer to evaluate changes in patients over time.

Development of temporal and distance parameters of gait in normal children.

Temporal and distance parameters of 33 normal children were obtained from instrumented gait analysis prospectively over five consecutive years. The parameters were normalised to minimise the confounding effects of increasing height and leg length. Rank correlations were performed on normalised speed, normalised stride length, normalised cadence and normalised walk ratio across consecutive pairs of years to examine the ranking of these parameters for an individual child over time. Consistent trends of increasing rank correlation were observed in normalised stride length and normalised walk ratio suggesting that individual children were continuing to adjust these gait parameters towards their own characteristic position within the normal range. Consistent trends were not observed in the rank correlations for normalised speed and normalised cadence. These findings support the concept that individual children predominantly adjusted their cadence to effect changes in speed, while the development of stride length was dictated by other factors specific to the individual child. Rank correlation coefficients for walk ratio between consecutive years increased from the ages of 7-11 years of age and hence walk ratio appears be a feature of gait that matures beyond the age of 7 years. This accords with the proposal that it is an invariant parameter for an individual.

Functional electrical stimulation to the dorsiflexors and quadriceps in children with cerebral palsy.

PURPOSE: To assess the effects of functional electrical stimulation (FES) of the ankle dorsiflexors and quadriceps in children with cerebral palsy. METHODS: Fourteen children (mean age 8 years) were randomly allocated to a treatment or control group. The treatment group received 2 weeks of neuromuscular electrical stimulation followed by 8 weeks of FES used at home and school. The control group continued with its usual physiotherapy program. Assessment took place at baseline and before and after the treatment period. Both control and treatment groups were fitted with FES for gait analysis at the second and final assessments. RESULTS: In both groups, FES of the ankle dorsiflexors resulted in a significant (p < 0.01) effect on gait kinematics. However, no long-term treatment effect of using FES for 8 weeks was found. CONCLUSIONS: FES for selected children with cerebral palsy, receiving adequate support, can be a practical treatment option to improve gait kinematics.

Correlation of the Edinburgh Gait Score with the Gillette Gait Index, the Gillette Functional Assessment Questionnaire, and dimensionless speed.

This study examines the correlation of the Edinburgh Gait Score (EGS) with the Gillette Gait Index (GGI; formerly the Normalcy Index), the Gillette Functional Assessment Questionnaire, and speed, all of which are used as measures of gait quality or function. Scores were computed for 58 subjects, all with a diagnosis of cerebral palsy. The correlation of the EGS with all of the other scores was found to be significant, with r2 ranging from 0.26 to 0.79. The strongest correlation was found with the GGI, which may reflect common features in the derivation of both of these scores, although the EGS was derived from observational gait analysis and the GGI from principal component analysis of variables from computerized 3-dimensional gait data. We conclude that the EGS shows good concurrent validity with alternative gait assessment scores.

Passive and dynamic rotation of the lower limbs in children with diplegic cerebral palsy.

Rotation characteristics in gait and passive rotation of the lower limbs were evaluated retrospectively in 105 patients with diplegic cerebral palsy (65 males, 40 females; mean age 13y [SD 6y 9mo]; range 4y 4mo-40y 5mo). Of 105 patients, 22 (20.9%) required crutches, sticks, tripods, or a K-walker for their daily ambulation. Twelve (11.5%) patients used a wheelchair or buggy for community distances, e.g. shopping. Significant differences in rotational characteristics were found at the pelvis, hip, knee, and foot between left and right legs. Patients who were more affected on the right (group R, n=33) or the left side (group L, n=39) were re-evaluated. There was also a group of patients who were not asymmetrically affected (group S, n=33). In group L, maximum passive internal rotation was significantly greater on the left side, while no difference between the sides was found in group R. Peak internal rotation in gait was significantly higher on the right side in group R, but did not differ significantly between the sides in group L. Right hindfoot-thigh angle and transmalleolar axis were more external on the right, irrespective of which leg was more affected. These findings may have implications for the early non-operative management of limb posture in infants with diplegia and the surgical management of established lower extremity malrotation.

Test-Retest repeatability of gluteus maximus strength testing using a fixed digital dynamometer in children with cerebral palsy.

OBJECTIVE: To investigate the test-retest repeatability of the measurement of the gluteus maximus strength using a fixed digital dynamometer. DESIGN: Test-retest design. The strength of the gluteus maximus was measured in prone position during 2 sessions an average of 6 days apart. SETTING: Gait analysis laboratory. PARTICIPANTS: Eleven children with spastic diplegic (n=10) and hemiplegic (n=1) cerebral palsy (CP), age 6 to 14 years, and 11 aged-matched children. All were able to walk independently, but 2 in the CP group used walking aids. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: On 2 occasions, gluteus maximus strength was measured 3 times in 2 positions of the hip joint. Repeatability of the measurements was assessed by intraclass correlation coefficients (ICCs), coefficients of variation, and the coefficient of repeatability. RESULTS: When normalized to body mass, children with CP had significantly less gluteus maximus strength compared with the controls. The ICCs for the control group ranged from .76 to .85 and from .75 to .83 for the involved leg in the CP group. CONCLUSIONS: The reliability of measurement of gluteus maximus strength was good for both control group and the involved leg of the CP group. The normalized values for gluteus maximus strength and measures of reproducibility can be used when measuring gluteus maximus strength in children with CP.

Edinburgh visual gait score for use in cerebral palsy.

Complex gait analysis systems are not generally available worldwide, and no simple system of assessing gait by observation has been validated specifically for use in patients with cerebral palsy. The authors have developed a visual gait analysis score for use in cerebral palsy. Videotaped sequences of patients were recorded before and after surgery as part of a three-dimensional gait study using a Vicon (Oxford, U.K.) gait analysis system. The score demonstrated good intraobserver and interobserver reliability. The numeric values of the score elements correlated well with the measurements obtained from instrumented gait analysis for the same patients, and the score was able to detect postoperative change.